Study of Safety and Drug Levels of CCI15106 Inhalation Powder in Healthy Adults and Adults With Moderate Chronic Obstructive Pulmonary Disease. Study of CCI15106 Levels in People Standing Near the Person Inhaling the Drug

NCT03235726 | Completed Phase 1 Results

• 2 other identifiers: 2058222017-001070-42
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

This single and repeat increasing dose study will collect information on safety, tolerability and drug levels in the body of the CCI15106 inhalation powder. The study will also look at the level of CCI15106 that will be released into the air and may be found in the blood of the people standing around the person inhaling it (bystanders). This is a two-part study in which Part 1 will enroll healthy subjects and look at environmental and bystander exposure and Part 2 will enroll subjects with moderate COPD. Approximately 36 healthy subjects and approximately 22 subjects with COPD will be randomized in this study for dosing. The total study duration will be 82 days for Cohort A Part 1; 75 days for Cohort B Part 1 and Cohort C Part 1; 77 days for Cohort A Part 2; and 90 days for Cohort B Part 2.

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

bystander; inhalation powder; monodose device; COPD; pharmacokinetics; safety; Healthy; CCI15106; tolerability

Outcome Measures

Primary Outcomes (72)

• Part 1 Cohort A: Number of Participants With Non-serious Adverse Events (NSAEs) and Serious Adverse Events (SAEs) in CCI15106

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations judged by physician. Safety population comprised of all participants who received at least one dose of study treatment during the study.

  Up to 51 days

• Part 1 Cohort B: Number of Participants With NSAEs and SAEs in CCI15106

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations judged by physician.

  Up to 46 days

• Part 1 Cohort C: Number of Participants With NSAEs and SAEs in Bystanders

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations judged by physician.

  Up to 46 days

• Part 2 Cohort A: Number of Participants With NSAEs and SAEs

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations judged by physician.

  Up to 33 days

• Part 2 Cohort B: Number of Participants With NSAEs and SAEs

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations judged by physician.

  Up to 46 days

• Part 1: Number of Participants With Hematology Values of Potential Clinical Importance (PCI) in CCI15106

  PCI ranges for the hematology parameters were as follows: hematocrit (high: \>0.54 proportion of red blood cell \[RBC\] in blood for male, \>0.54 proportion of RBC in blood for female), hemoglobin (high: \>180 grams \[g\]/L in male, \>180 g/L in female), lymphocytes (low: \<0.8 10\^9/L), neutrophil count (low: \<1.5 10\^9/L) and platelet count (low: \<100 10\^9/L and high: 550 10\^9/L). Data for the participants with high and low values has been reported.

  Up to 51 days

• Part 1: Number of Participants With Hematology Values of PCI in Bystanders

  PCI ranges for the hematology parameters were as follows: hematocrit (high: \>0.54 proportion of RBC in blood for male, \>0.54 proportion of RBC in blood for female), hemoglobin (high: \>180 g/L in male, \>180 g/L in female), lymphocytes (low: \<0.8 10\^9/L), neutrophil count (low: \<1.5 10\^9/L) and platelet count (low: \<100 10\^9/L and high: 550 10\^9/L). Data for the participants with high and low values has been reported.

  Up to 46 days

• Part 2: Number of Participants With Hematology Values of PCI

  PCI ranges for the hematology parameters were as follows: hematocrit (high: \>0.54 proportion of RBC in blood for male, \>0.54 proportion of RBC in blood for female), hemoglobin (high: \>180 g/L in male, \>180 g/L in female), lymphocytes (low: \<0.8 10\^9/L), neutrophil count (low: \<1.5 10\^9/L) and platelet count (low: \<100 10\^9/L and high: 550 10\^9/L). Data for the participants with high and low values has been reported.

  Up to 46 days

• Part 1: Number of Participants With Clinical Chemistry Values of PCI in CCI15106

  PCI ranges for the clinical chemistry parameters were as follows: albumin (low: \<30 millimole per liter \[mmol/L\]), calcium (low: \<2 mmol/L and high: \>2.75 mmol/L), glucose (low: \<3 mmol/L and high: \>9 mmol/L), potassium (low: \<3 mmol/L and high: \>5.5 mmol/L) and sodium (low: \<130 mmol/L and high: \>150 mmol/L). Data for the participants with high and low values has been reported.

  Up to 51 days

• Part 1: Number of Participants With Clinical Chemistry Values of PCI in Bystanders

  PCI ranges for the clinical chemistry parameters were as follows: albumin (low: \<30 mmol/L), calcium (low: \<2 mmol/L and high: \>2.75 mmol/L), glucose (low: \<3 mmol/L and high: \>9 mmol/L), potassium (low: \<3 mmol/L and high: \>5.5 mmol/L) and sodium (low: \<130 mmol/L and high: \>150 mmol/L). Data for the participants with high and low values has been reported.

  Up to 46 days

• Part 2: Number of Participants With Clinical Chemistry Values of PCI

  PCI ranges for the clinical chemistry parameters were as follows: albumin (low: \<30 mmol/L), calcium (low: \<2 mmol/L and high: \>2.75 mmol/L), glucose (low: \<3 mmol/L and high: \>9 mmol/L), potassium (low: \<3 mmol/L and high: \>5.5 mmol/L) and sodium (low: \<130 mmol/L and high: \>150 mmol/L). Data for the participants with high and low values has been reported.

  Up to 46 days

• Part 1 Cohort A: Potential of Hydrogen (pH) Value by Visit- CCI15106 60 mg SD

  Urine samples were collected from participants at indicated time points for analysis of pH. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1).

  Baseline (Day -1) and Day 2

• Part 1 Cohort A: pH Value by Visit- CCI15106 120 mg SD

  Urine sample was collected from participants at indicated time point for analysis of pH.

  Day 5

• Part 1 Cohort A: pH Value by Visit- CCI15106 30 mg BID

  Urine samples were collected from participants at indicated time points for analysis of pH.

  Days 12 and 22

• Part 1 Cohort B: pH Value by Visit- CCI15106 60 mg BID

  Urine samples were collected from participants at indicated time points for analysis of pH. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1).

  Baseline (Day -1), Days 7 and 15

• Part 1: pH Value by Visit- Placebo

  Urine samples were collected from participants at indicated time points for analysis of pH. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1).

  Baseline (Day -1), Days 2, 5, 7, 12, 15 and 22

• Part 1 Cohort C: pH Value by Visit- CCI15106 in Bystanders

  Urine samples were collected from participants at indicated time points for analysis of pH. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1).

  Baseline (Day -1), Days 7 and 15

• Part 2 Cohort A: pH Value by Visit- CCI15106

  Urine samples were collected from participants at indicated time points for analysis of pH. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1).

  Baseline (Day -1) and Day 2

• Part 2 Cohort B: pH Value by Visit- CCI15106 60 mg BID

  Urine samples were collected from participants at indicated time points for analysis of pH. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1).

  Baseline (Day -1), Days 7 and 15

• Part 1 Cohort A: Specific Gravity Value by Visit- CCI15106 60 mg SD

  Urinary specific gravity measurement is a routine part of urinalysis. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. Urine samples were collected from participants at indicated time points for analysis of specific gravity. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1).

  Baseline (Day -1) and Day 2

• Part 1 Cohort A: Specific Gravity Value by Visit- CCI15106 120 mg SD

  Urinary specific gravity measurement is a routine part of urinalysis. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. Urine sample was collected from participants at indicated time point for analysis of specific gravity.

  Day 5

• Part 1 Cohort A: Specific Gravity Value by Visit- CCI15106 30 mg BID

  Urinary specific gravity measurement is a routine part of urinalysis. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. Urine samples were collected from participants at indicated time points for analysis of specific gravity.

  Days 12 and 22

• Part 1 Cohort B: Specific Gravity Value by Visit- CCI15106 60 mg BID

  Urinary specific gravity measurement is a routine part of urinalysis. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. Urine samples were collected from participants at indicated time points for analysis of Specific gravity. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1).

  Baseline (Day -1), Days 7 and 15

• Part 1: Specific Gravity Value by Visit- Placebo

  Urinary specific gravity measurement is a routine part of urinalysis. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. Urine samples were collected from participants at indicated time points for analysis of Specific gravity. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1).

  Baseline (Day -1), Days 2, 5, 7, 12, 15 and 22

• Part 1 Cohort C: Specific Gravity Value by Visit- CCI15106 in Bystanders

  Urinary specific gravity measurement is a routine part of urinalysis. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. Urine samples were collected from participants at indicated time points for analysis of specific gravity. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1).

  Baseline (Day -1), Days 7 and 15

• Part 2 Cohort A: Specific Gravity Value by Visit- CCI15106

  Urinary specific gravity measurement is a routine part of urinalysis. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. Urine samples were collected from participants at indicated time points for analysis of specific gravity. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1).

  Baseline (Day -1) and Day 2

• Part 2 Cohort B: Specific Gravity Value by Visit- CCI15106 60 mg BID

  Urinary specific gravity measurement is a routine part of urinalysis. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. Urine samples were collected from participants at indicated time points for analysis of specific gravity. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1).

  Baseline (Day -1), Days 7 and 15

• Part 1: Number of Participants With Worst Case Post-Baseline 12-lead Electrocardiogram (ECG) of PCI in CCI15106

  PCI ranges for the ECG parameters were as follows: absolute QTc interval \>450 and \<480, \>=480 and \<500, \>=500 milliseconds (msec), absolute PR interval \<110 and \>220 msec and absolute QRS interval \<75 and \>110 msec. QTcF=Frederica's QT interval corrected for heart rate; QTcB=Bazett's QT interval corrected for heart rate. Data for worst case post-Baseline has been reported.

  Up to 51 days

• Part 1: Number of Participants With Worst Case Post-Baseline 12-lead ECG of PCI in Bystander

  PCI ranges for the ECG parameters were as follows: absolute QTc interval \>450 and \<480, \>=480 and \<500, \>=500 msec, absolute PR interval \<110 and \>220 msec and absolute QRS interval \<75 and \>110 msec. Data for worst case post-Baseline has been reported.

  Up to 46 days

• Part 2: Number of Participants With Worst Case Post-Baseline 12-lead ECG of PCI

  PCI ranges for the ECG parameters were as follows: absolute QTc interval \>450 and \<480, \>=480 and \<500, \>=500 msec, absolute PR interval \<110 and \>220 msec and absolute QRS interval \<75 and \>110 msec. Data for worst case post-Baseline has been reported.

  Up to 46 days

• Part 1: Number of Participants With Abnormal Telemetry Findings

  Continuous cardiac telemetry was performed from approximately 0.5 hour (pre-dose) to 4 hours post-dose. Abnormal findings were categorized as clinically significant (CS) and not clinically significant (NCS). Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.

  Days 1, 3, 6, 7, 12 and 18: 0.5 hour (pre-dose) to 4 hours post-dose

• Part 2: Number of Participants With Abnormal Telemetry Findings

  Continuous cardiac telemetry was performed from approximately 0.5 hour (pre-dose) to 4 hours post-dose. Abnormal findings were categorized as CS and NCS. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.

  Days 1, 7, 12 and 13: 0.5 hour (pre-dose) to 4 hours post-dose

• Part 1: Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Indicated Time Points

  FEV1 is a measure of lung function and the maximal amount of air that can be forcefully exhaled in one second. FEV1 was measured using standard spirometry. Percent predicted FEV1 was calculated as: Percent predicted FEV1=(maximum FEV1 divided by predicted normal FEV1)\*100.

  Days 1, 3, 6 and 19: pre-dose, 0.25, 0.5, 1 and 4 hours post-dose; Days 8, 11 and 16: pre-dose and 4 hours post-dose; Day 14: pre-dose, 0.5, 1 and 4 hours post-dose

• Part 1: Percent Predicted Forced Vital Capacity (FVC) at Indicated Time Points

  FVC is a measure of lung function and the maximal amount of air that can be forcefully exhaled in one second. FVC was measured using standard spirometry. Percent predicted FVC was calculated as: Percent predicted FVC=(maximum FVC divided by predicted normal FVC)\*100.

  Days 1, 3, 6 and 19: pre-dose, 0.25, 0.5, 1 and 4 hours post-dose; Days 8, 11 and 16: pre-dose and 4 hours post-dose; Day 14: pre-dose, 0.5, 1 and 4 hours post-dose

• Part 2: Percent Predicted FEV1 at Indicated Time Points

  FEV1 is a measure of lung function and the maximal amount of air that can be forcefully exhaled in one second. FEV1 was measured using standard spirometry. Percent predicted FEV1 was calculated as: Percent predicted FEV1=(maximum FEV1 divided by predicted normal FEV1)\*100.

  Day 1 and 14: pre-dose, 0.25, 0.5, 1 and 4 hours post-dose; Days 3, 6 and 11: pre-dose and 4 hours post-dose

• Part 2: Percent Predicted FVC at Indicated Time Points

  FVC is a measure of lung function and the maximal amount of air that can be forcefully exhaled in one second. FVC was measured using standard spirometry. Percent predicted FVC was calculated as: Percent predicted FVC=(maximum FVC divided by predicted normal FVC)\*100.

  Day 1 and 14: pre-dose, 0.25, 0.5, 1 and 4 hours post-dose; Days 3, 6 and 11: pre-dose and 4 hours post-dose

• Part 1: Number of Participants With Vital Signs Values of PCI

  PCI ranges for the vital signs parameters were as follows: systolic blood pressure (SBP) \<85 and \>160 millimeters of mercury (mmHg), diastolic blood pressure (DBP) \<45 and \>100 mmHg and heart rate \<40 and \>110 beats per minute (bpm). Data for the participants with high and low values has been reported.

  Up to 51 days

• Part 1: Number of Participants With Vital Signs Values of PCI in Bystanders

  PCI ranges for the vital signs parameters were as follows: SBP \<85 and \>160 mmHg, DBP \<45 and \>100 mmHg and heart rate \<40 and \>110 bpm. Data for the participants with high and low values has been reported.

  Up to 46 days

• Part 2: Number of Participants With Vital Signs Values of PCI

  PCI ranges for the vital signs parameters were as follows: SBP \<85 and \>160 mmHg, DBP \<45 and \>100 mmHg and heart rate \<40 and \>110 bpm. Data for the participants with high and low values has been reported.

  Up to 46 days

• Part 1 Cohort A: Area Under the Curve (AUC) From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-t]) After Single Dose Administration of CCI15106 60 mg on Day 1

  Blood samples were collected to evaluate the pharmacokinetics (PKs) of CCI15106 at the indicated time points on Day 1 for the analysis of AUC(0-t) data. PK population consisted of participants who received at least one dose of study treatment and who undergo plasma PK sampling and had at least one post-dose concentration result.

  Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24 and 48 hours post-dose

• Part 1 Cohort A: AUC(0-t) After Single Dose Administration of CCI15106 120 mg on Day 3

  Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 3 for the analysis of AUC(0-t) data.

  Day 3: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24, 48 and 72 hours post-dose

• Part 2 Cohort A: AUC(0-t) After Single Dose Administration of CCI15106 60 mg on Day 1

  Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 1 for the analysis of AUC(0-t) data.

  Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 and 24 hours post-dose

• Part 1 Cohort A: Maximum Observed Plasma Concentration (Cmax) After Single Dose Administration of CCI15106 60 mg on Day 1

  Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 1 for the analysis of Cmax data.

  Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24 and 48 hours post-dose

• Part 1 Cohort A: Cmax After Single Dose Administration of CCI15106 120 mg on Day 3

  Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 3 for the analysis of Cmax data.

  Day 3: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24, 48 and 72 hours post-dose

• Part 2 Cohort A: Cmax After Single Dose Administration of CCI15106 60 mg on Day 1

  Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 1 for the analysis of Cmax data.

  Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 and 24 hours post-dose

• Part 1 Cohort A: Time of Maximum Concentration (Tmax) After Single Dose Administration of CCI15106 60 mg on Day 1

  Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 1 for the analysis of tmax data.

  Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24 and 48 hours post-dose

• Part 1 Cohort A: Tmax After Single Dose Administration of CCI15106 120 mg on Day 3

  Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 3 for the analysis of tmax data.

  Day 3: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24, 48 and 72 hours post-dose

• Part 2 Cohort A: Tmax After Single Dose Administration of CCI15106 60 mg on Day 1

  Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 1 for the analysis of tmax data.

  Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 and 24 hours post-dose

• Part 1 Cohort A: AUC From Time Zero to Infinity (AUC[0-infinity]) After Single Dose Administration of CCI15106 60 mg on Day 1

  Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 1 for the analysis of AUC(0-infinity) data.

  Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24 and 48 hours post-dose

• Part 1 Cohort A: AUC(0-infinity) After Single Dose Administration of CCI15106 120 mg on Day 3

  Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 3 for the analysis of AUC(0-infinity) data.

  Day 3: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24, 48 and 72 hours post-dose

• Part 2 Cohort A: AUC(0-infinity) After Single Dose Administration of CCI15106 60 mg on Day 1

  Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 1 for the analysis of AUC(0-infinity) data.

  Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 and 24 hours post-dose

• Part 1 Cohort A: Elimination Half-life (t1/2) After Single Dose Administration of CCI15106 60 mg on Day 1

  Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 1 for the analysis of t1/2 data.

  Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24 and 48 hours post-dose

• Part 1 Cohort A: t1/2 After Single Dose Administration of CCI15106 120 mg on Day 3

  Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 3 for the analysis of t1/2 data.

  Day 3: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24, 48 and 72 hours post-dose

• Part 2 Cohort A: t1/2 After Single Dose Administration of CCI15106 60 mg on Day 1

  Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 1 for the analysis of t1/2 data.

  Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 and 24 hours post-dose

• Part 1 Cohort A: Clearance (CL/F) After Single Dose Administration of CCI15106 60 mg on Day 1

  Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 1 for the analysis of CL/F data.

  Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24 and 48 hours post-dose

• Part 1 Cohort A: CL/F After Single Dose Administration of CCI15106 120 mg on Day 3

  Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 3 for the analysis of CL/F data.

  Day 3: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24, 48 and 72 hours post-dose

• Part 2 Cohort A: CL/F After Single Dose Administration of CCI15106 60 mg on Day 1

  Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Day 1 for the analysis of CL/F data.

  Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 and 24 hours post-dose

• Part 1 Cohort A: AUC From Time Zero to End of Dosing Interval (AUC[0-tau]) After Repeated Dose Administration of CCI15106 30 mg

  Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Days 6 and 19 for the analysis of AUC(0-tau) data.

  Day 6: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 12 hours post-dose; Day 19: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24, 48 and 72 hours post-dose

• Part 1 Cohort B: AUC(0-tau) After Repeated Dose Administration of CCI15106 60 mg

  Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Days 1 and 14 for the analysis of AUC(0-tau) data.

  Days 1 and 14: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 12 hours post-dose

• Part 2 Cohort B: AUC(0-tau) After Repeated Dose Administration of CCI15106 60 mg

  Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Days 1 and 14 for the analysis of AUC(0-tau) data.

  Days 1 and 14: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 12 hours post-dose

• Part 1 Cohort A: Cmax After Repeated Dose Administration of CCI15106 30 mg

  Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Days 6 and 19 for the analysis of Cmax data.

  Day 6: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 12 hours post-dose; Day 19: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24, 48 and 72 hours post-dose

• Part 1 Cohort B: Cmax After Repeated Dose Administration of CCI15106 60 mg

  Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Days 1 and 14 for the analysis of Cmax data.

  Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 12 hours post-dose; Day 14: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 and 24 hours post-dose

• Part 2 Cohort B: Cmax After Repeated Dose Administration of CCI15106 60 mg

  Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Days 1 and 14 for the analysis of Cmax data.

  Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 12 hours post-dose; Day14: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 and 24 hours post-dose

• Part 1 Cohort A: Tmax After Repeated Dose Administration of CCI15106 30 mg

  Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Days 6 and 19 for the analysis of tmax data.

  Day 6: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 12 hours post-dose; Day 19: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24, 48 and 72 hours post-dose

• Part 1 Cohort B: Tmax After Repeated Dose Administration of CCI15106 60 mg

  Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Days 1 and 14 for the analysis of tmax data.

  Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 12 hours post-dose; Day 14: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 and 24 hours post-dose

• Part 2 Cohort B: Tmax After Repeated Dose Administration of CCI15106 60 mg

  Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Days 1 and 14 for the analysis of tmax data.

  Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 12 hours post-dose; Day14: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 and 24 hours post-dose

• Part 1 Cohort A: t1/2 After Repeated Dose Administration of CCI15106 30 mg

  Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Days 6 and 19 for the analysis of t1/2 data.

  Day 6: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 12 hours post-dose; Day 19: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24, 48 and 72 hours post-dose

• Part 1 Cohort B: t1/2 After Repeated Dose Administration of CCI15106 60 mg

  Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Days 1 and 14 for the analysis of t1/2 data.

  Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 12 hours post-dose; Day 14: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 and 24 hours post-dose

• Part 2 Cohort B: t1/2 After Repeated Dose Administration of CCI15106 60 mg

  Blood samples were collected to evaluate the PKs of CCI15106 at the indicated time points on Days 1 and 14 for the analysis of t1/2 data.

  Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 12 hours post-dose; Day14: pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 and 24 hours post-dose

• Part 1: Concentration of CCI15106 in Plasma of Bystanders: Cohort C

  Blood samples were collected from bystanders 15 minutes after dosing at indicated time points. Bystander PK population consisted of participants who were present at least once in the room with the participant receiving the dose, undergo plasma PK sampling and had post-dose concentration result.

  Days 1, 7 and 14: pre-dose, 15 minutes post-dose

• Part 1: Concentration of CCI15106 Accumulated on Filters Fitted on Bystander: Cohort C

  Personal exposure air samples were collected on filters placed on each bystander after the first daily dose at indicated time points. The filters were used to measure CCI15106 concentration in the person's breathing zone. Fixed location concentrations were measured near window, near door, back to wall and facing wall in the dosing room over 15 minutes post-dose. Each bystander had a filter attached to their study clothing. The filters were measured for CCI15106. This was a single measurement from the filter for each bystsander. The locations (near window, near door, back to wall and facing wall) were just to record where the bystander was located in the room.

  Days 1, 7 and 14: 15 minutes post-dose

• Part 1: Concentration of CCI15106 Accumulated on Filters Fitted on Stationary Pumps: Cohort C

  Static air samples were collected on filters within air pumps positioned in two locations (bench and corner) in the room. Sampling devices attached to sampling pumps were used to measure CCI15106 concentration. Fixed location concentrations were measured in corner of room and on bench at back of room over 20 minutes and 60 minutes post-dosing.

  Days 1, 7 and 14: 20 and 60 minutes post-dose

Secondary Outcomes (3)

• Part 1: Concentration of CCI15106 in Lung Epithelial Lining Fluid (ELF) in Repeated Dose of Cohort B 60 mg

  Up to Day 13

• Part 2: Concentration of CCI15106 in ELF in Repeated Dose of Cohort B 60 mg

  Up to Day 13

• Part 1: Number of Participants With Medical Device Incidents in CCI15106

  Up to Day 19

Study Arms (9)

Cohort A, Part 1: Active

EXPERIMENTAL

60 milligrams (mg) single dose of CCI15106 will be administered by inhalation route on Day 1; 120 mg single dose will be administered on Day 3; and then 30 mg dose will be administered twice daily (BID) on Days 6-19 to healthy subjects.

Drug: CCI15106

Cohort A, Part 1: Placebo

PLACEBO COMPARATOR

60 mg single dose of placebo will be administered by inhalation route on Day 1; 120 mg single dose will be administered on Day 3; and then 30 mg dose will be administered BID on Days 6-19 to healthy subjects.

Drug: Placebo

Cohort B, Part 1: Active

EXPERIMENTAL

60 mg of CCI15106 BID will be administered by inhalation route for 14 days to healthy subjects.

Drug: CCI15106

Cohort B, Part 1: Placebo

PLACEBO COMPARATOR

60 mg of placebo BID will be administered by inhalation route for 14 days to healthy subjects.

Drug: Placebo

Cohort C, Part 1: bystanders

NO INTERVENTION

Healthy subjects will be enrolled to follow bystander exposure and will be studied concomitantly with Cohort B.

Cohort A, Part 2: Active

EXPERIMENTAL

60 mg single dose of CCI15106 will be administered by inhalation route to subjects with COPD.

Drug: CCI15106

Cohort A, Part 2: Placebo

PLACEBO COMPARATOR

60 mg single dose of placebo will be administered by inhalation route to subjects with COPD.

Drug: Placebo

Cohort B, Part 2: Active

EXPERIMENTAL

60 mg BID dose of CCI15106 will be administered by inhalation route for 14 days to subjects with COPD.

Drug: CCI15106

Cohort B, Part 2: Placebo

PLACEBO COMPARATOR

60 mg BID dose of placebo will be administered by inhalation route for 14 days to subjects with COPD.

Drug: Placebo

Interventions

CCI15106 DRUG

One capsule (single dose or repeat dose) of 30 mg of CCI15106 will be administered to healthy subjects and subjects with COPD via inhalation route using Monodose RS01 device. The morning dose will be taken in fasting state and for repeat dose; the evening dose will be taken at least 2 hours after food.

Cohort A, Part 1: Active; Cohort A, Part 2: Active; Cohort B, Part 1: Active; Cohort B, Part 2: Active

Placebo DRUG

One capsule of placebo will be administered to healthy subjects and subjects with COPD via inhalation route using Monodose RS01 device. The morning dose will be taken in fasting state and for repeat dose; the evening dose will be taken at least 2 hours after food.

Cohort A, Part 1: Placebo; Cohort A, Part 2: Placebo; Cohort B, Part 1: Placebo; Cohort B, Part 2: Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For healthy subjects and bystanders:
• to 65 years of age.
• Healthy as determined by a doctor.
• Men who agree to use contraception during the treatment period and for at least 7 months after the last dose of study medicine and agree not to donate sperm during this period.
• Women who are not pregnant or breastfeeding, and not of childbearing potential.
• For subjects with COPD:
• to 75 years of age.
• Diagnosed with moderate COPD by a doctor.
• Have breathing test results that are consistent with moderate COPD as defined in the study protocol.
• A smoker or an ex-smoker.
• Men who agree to use contraception during the treatment period and for at least 7 months after the last dose of study medicine and agree not to donate sperm during this period.
• Women who are not pregnant or breastfeeding, and not of childbearing potential.

You may not qualify if:

• For healthy subjects and bystanders:
• History of liver disease.
• Use of over-the-counter or prescription drugs (including vitamins) 7 days before the study until completion of the follow-up visit.
• Participation in the study would result in loss of more than 500 milliliter (mL) of blood within 3 months.
• Participation in another clinical trial with an investigational product within about 3 months before this study.
• Positive drug/alcohol screen.
• Regular use of known drugs of abuse.
• Regular alcohol consumption within 3 months before the study.
• Breath test indicative of smoking at study start.
• Documented lactose allergy/intolerance.
• Men whose partner is pregnant or breastfeeding cannot participate.
• Certain blood test results may not allow subjects to participate, as described in the study protocol.
• For subjects with COPD:
• History of liver disease.
• Poorly controlled COPD disease as, for example, more than 2 exacerbations of COPD per year.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Park Royal, London, NE10 7EW, United Kingdom

Location

Related Publications (1)

• Dumont EF, Oliver AJ, Ioannou C, Billiard J, Dennison J, van den Berg F, Yang S, Chandrasekaran V, Young GC, Lahiry A, Starbuck DC, Harrell AW, Georgiou A, Hopchet N, Gillies A, Baker SJ. A Novel Inhaled Dry-Powder Formulation of Ribavirin Allows for Efficient Lung Delivery in Healthy Participants and Those with Chronic Obstructive Pulmonary Disease in a Phase 1 Study. Antimicrob Agents Chemother. 2020 Apr 21;64(5):e02267-19. doi: 10.1128/AAC.02267-19. Print 2020 Apr 21.

  PMID: 32071044 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This is a double blind, randomized study and subject and investigator will be blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: In this study, subjects will be randomized to receive either study drug or placebo in a parallel manner.

Study Record Dates

• First Submitted: July 11, 2017
• First Posted: August 1, 2017
• Study Start: July 13, 2017
• Primary Completion: June 19, 2018
• Study Completion: June 19, 2018
• Last Updated: July 8, 2020
• Results First Posted: September 27, 2019

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

GB (1)