Dose Escalating Study of CCI15106 Inhalation Capsules in Healthy Subjects and Moderate Chronic Obstructive Pulmonary Disease (COPD) Patients

NCT03243760 | Terminated Phase 1

• 2 other identifiers: 2020312015-003960-35
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This study will be the first administration of CCI15106 capsules for inhalation to humans. The primary objective of the study is to investigate the safety and tolerability of single and repeat escalating doses of CCI15106 in healthy subjects and patients with moderate chronic obstructive pulmonary disease (COPD). The intention of this study is to provide sufficient confidence in the safety of the molecule delivered by inhalation to inform progression to further repeat dose and proof of concept studies. This will be a three-part study. Part 1 will investigate single ascending doses and Part 2 repeat ascending doses in healthy subjects. In Part 3, a single dose will be administered to patients with moderate COPD. There will be screening period of up to 30 days. The treatment period will be 3 days for Parts 1 and 3 and 16 days for Part 2. Follow-up will be performed within 30 days after the last dose.

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

CCI15106; pharmacokinetics; BAL; COPD

Outcome Measures

Primary Outcomes (48)

• Part 1: Number of participants with adverse events (AE)

  An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AE will be collected from the start of study treatment until the final follow-up visit.

  Up to 33 days

• Part 2: Number of participants with AE

  An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AE will be collected from the start of study treatment until the final follow-up visit.

  Up to 46 days

• Part 3: Number of participants with AE

  An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AE will be collected from the start of study treatment until the final follow-up visit.

  Up to 33 days

• Part 1: Number of subjects with abnormal clinical hematology test findings

  Hematology tests will be performed as a measure of safety

  Up to 33 days

• Part 2: Number of subjects with abnormal clinical hematology test findings

  Hematology tests will be performed as a measure of safety

  Up to 46 days

• Part 3: Number of subjects with abnormal clinical hematology test findings

  Hematology tests will be performed as a measure of safety

  Up to 33 days

• Part 1: Number of subjects with abnormal clinical chemistry test findings

  Clinical chemistry laboratory tests will be performed as a measure of safety

  Up to 33 days

• Part 2: Number of subjects with abnormal clinical chemistry test findings

  Clinical chemistry laboratory tests will be performed as a measure of safety

  Up to 46 days

• Part 3: Number of subjects with abnormal clinical chemistry test findings

  Clinical chemistry laboratory tests will be performed as a measure of safety

  Up to 33 days

• Part 1: Number of subjects with abnormal urine analysis test findings

  Urine analysis tests will be performed as a measure of safety

  Up to 33 days

• Part 2: Number of subjects with abnormal urine analysis test findings

  Urine analysis tests will be performed as a measure of safety

  Up to 46 days

• Part 3: Number of subjects with abnormal urine analysis test findings

  Urine analysis tests will be performed as a measure of safety

  Up to 33 days

• Part 1: Number of subjects with abnormal findings of body temperature

  Body temperature will be measured in a semi-supine position after 5 minutes of rest

  Up to 33 days

• Part 2: Number of subjects with abnormal findings of body temperature

  Body temperature will be measured in a semi-supine position after 5 minutes of rest

  Up to 46 days

• Part 3: Number of subjects with abnormal findings of body temperature

  Body temperature will be measured in a semi-supine position after 5 minutes of rest

  Up to 33 days

• Part 1: Number of subjects with abnormal blood pressure values

  Systolic and diastolic blood pressure values will be measured in a semi-supine position after 5 minutes of rest

  Up to 33 days

• Part 2: Number of subjects with abnormal blood pressure values

  Systolic and diastolic blood pressure values will be measured in a semi-supine position after 5 minutes of rest

  Up to 46 days

• Part 3: Number of subjects with abnormal blood pressure values

  Systolic and diastolic blood pressure values will be measured in a semi-supine position after 5 minutes of rest

  Up to 33 days

• Part 1: Number of subjects with abnormal pulse rate values

  Pulse rate will be measured in a semi-supine position after 5 minutes of rest

  Up to 33 days

• Part 2: Number of subjects with abnormal pulse rate values

  Pulse rate will be measured in a semi-supine position after 5 minutes of rest

  Up to 46 days

• Part 3: Number of subjects with abnormal pulse rate values

  Pulse rate will be measured in a semi-supine position after 5 minutes of rest

  Up to 33 days

• Part 1: Number of subjects with abnormal respiratory rate values

  Respiratory rate will be measured in a semi-supine position after 5 minutes of rest

  Up to 33 days

• Part 2: Number of subjects with abnormal respiratory rate values

  Respiratory rate will be measured in a semi-supine position after 5 minutes of rest

  Up to 46 days

• Part 3: Number of subjects with abnormal respiratory rate values

  Respiratory rate will be measured in a semi-supine position after 5 minutes of rest

  Up to 33 days

• Part 1: Number of subjects with abnormal electrocardiogram (ECG) findings

  12-lead ECG will be obtained during the study in semi-supine position after 5 minutes rest.

  Up to 33 days

• Part 2: Number of subjects with abnormal ECG findings

  12-lead ECG will be obtained during the study in semi-supine position after 5 minutes rest.

  Up to 46 days

• Part 3: Number of subjects with abnormal ECG findings

  12-lead ECG will be obtained during the study in semi-supine position after 5 minutes rest.

  Up to 33 days

• Part 1: Number of subjects with abnormal Telemetry findings

  Cardiac telemetry will be performed continuously till 4hour post morning dose.

  Up to 33 days

• Part 2: Number of subjects with abnormal telemetry findings

  Cardiac telemetry will be performed continuously till 4hour post morning dose.

  Up to 46 days

• Part 3: Number of subjects with abnormal telemetry findings

  Cardiac telemetry will be performed continuously till 4hour post morning dose.

  Up to 33 days

• Part 1: Number of subjects with abnormal spirometry findings

  Spirometry is a test to diagnose lung conditions. Spirometry will be performed at selected time points during the study.

  Up to 4 hour post-dose

• Part 2: Number of subjects with abnormal spirometry findings

  Spirometry is a test to diagnose lung conditions. Spirometry will be performed at selected time points during the study.

  Up to 14 days

• Part 3: Number of subjects with abnormal spirometry findings

  Spirometry is a test to diagnose lung conditions. Spirometry will be performed at selected time points during the study.

  Up to 4 hour post dose

• Part 1: Area under the curve (AUC) from time zero to infinity (AUC[0-inf] following single dose administration of CCI15106

  Blood samples will be collected at specific time points to evaluate AUC(0-inf) of drug

  Pre dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24 hour post-dose and on follow-up

• Part 3: AUC[0-inf] following single dose administration of CCI15106

  Blood samples will be collected at specific time points to evaluate AUC(0-inf) of drug

  Pre dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24 hour post-dose and on follow-up

• Part 1: AUC from time zero to the time of last quantifiable concentration (AUC[0-last]) following single dose administration of CCI15106

  Blood samples will be collected at specific time points to evaluate AUC(0-last) of drug

  Pre dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24 hour post-dose and on follow-up

• Part 3: AUC[0-last] following single dose administration of CCI15106

  Blood samples will be collected at specific time points to evaluate AUC(0-last) of drug

  Pre dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24 hour post-dose and on follow-up

• Part 1: Maximum plasma concentration (Cmax) following single dose administration of CCI15106

  Blood samples will be collected at specific time points to evaluate Cmax of drug

  Pre dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24 hour post-dose and on follow-up

• Part 2: Cmax following repeat dose administration of CCI15106

  Blood samples will be collected at specific time points to evaluate Cmax of drug

  Pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 hours post dose on Day 1 and 14; Pre-dose on Day 2-12 and on follow-up

• Part 3: Cmax following single dose administration of CCI15106

  Blood samples will be collected at specific time points to evaluate Cmax of drug

  Pre dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24 hour post-dose and on follow-up

• Part 1: time of maximum concentration (Tmax) following single dose administration of CCI15106

  Blood samples will be collected at specific time points to evaluate Tmax of drug

  Pre dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24 hour post-dose and on follow-up

• Part 2: Tmax following repeat dose administration of CCI15106

  Blood samples will be collected at specific time points to evaluate Tmax of drug

  Pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 hours post dose on Day 1 and 14; Pre-dose on Day 2-12 and on follow-up

• Part 3: Tmax following single dose administration of CCI15106

  Blood samples will be collected at specific time points to evaluate Tmax of drug

  Pre dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24 hour post-dose and on follow-up

• Part 1: Elimination half life (T1/2) following single dose administration of CCI15106

  Blood samples will be collected at specific time points to evaluate T1/2 of drug

  Pre dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24 hour post-dose and on follow-up

• Part 3: T1/2 following single dose administration of CCI15106

  Blood samples will be collected at specific time points to evaluate T1/2 of drug

  Pre dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24 hour post-dose and on follow-up

• Part 1: Clearance (CL/F) following single dose administration of CCI15106

  Clearance will be calculated from concentration-time curve based on each individual subject's profile.

  Pre dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24 hour post-dose and on follow-up

• part 3: CL/F following single dose administration of CCI15106

  Clearance will be calculated from concentration-time curve based on each individual subject's profile.

  Pre dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24 hour post-dose and on follow-up

• Part 2: AUC from time zero to end of dosing interval (AUC[0-tau]) following repeat dose administration of CCI15106

  Blood samples will be collected at specific time points to evaluate AUC(0-tau) of drug

  Pre-dose, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 hours post dose on Day 1 and 14; Pre-dose on Day 2-12 and on follow-up

Secondary Outcomes (5)

• Part 1 Concentrations of CCI15106 in ELF and BAL cell pellet

  Up to 2 hour post-dose

• Part 2: Concentrations of CCI15106 in ELF and BAL cell pellet

  Up to 13 days

• Part 1: Number of medical device incidents

  Day 1

• Part 2: Number of medical device incidents

  Up to 14 days

• Part 3: Number of medical device incidents

  Day 1

Study Arms (11)

Cohort A: Single dose CCI15106 7.5 mg /Placebo

EXPERIMENTAL

Healthy subjects will receive single dose of either 1 capsule CCI15106 7.5 milligram (mg) or matching placebo by inhalation via Modified Air Inlet Rotahaler™ device according to randomization.

Drug: CCI15106 7.5 mg capsule; Drug: Placebo; Drug: Placebo-2

Cohort B: Single dose CCI15106 15 mg /Placebo

EXPERIMENTAL

Healthy subjects will receive single dose of either 15 mg CCI15106 (2 capsules of 7.5 mg) or matching placebo by inhalation via Modified Air Inlet Rotahaler™ device according to randomization.

Drug: CCI15106 7.5 mg capsule; Drug: Placebo; Drug: Placebo-2

Cohort C: Single dose CCI15106 30 mg /Placebo

EXPERIMENTAL

Healthy subjects will receive single dose of either 30 mg CCI15106 (4 capsules of 7.5 mg) or matching placebo by inhalation via Modified Air Inlet Rotahaler™ device according to randomization.

Drug: CCI15106 7.5 mg capsule; Drug: Placebo; Drug: Placebo-2

Cohort D: Single dose CCI15106 30 mg /Placebo-BAL

EXPERIMENTAL

Healthy subjects will receive single dose of either 30 mg CCI15106 (4 capsules of 7.5 mg) or matching placebo by inhalation via Modified Air Inlet Rotahaler™ device according to randomization. BAL procedures will be performed in this cohort additionally.

Drug: CCI15106 7.5 mg capsule; Drug: Placebo; Drug: Placebo-2

Cohort E: Single dose CCI15106 45 mg /Placebo

EXPERIMENTAL

Healthy subjects will receive single dose of either 45 mg CCI15106 (6 capsules of 7.5 mg) or matching placebo by inhalation via Modified Air Inlet Rotahaler™ device according to randomization.

Drug: CCI15106 7.5 mg capsule; Drug: Placebo; Drug: Placebo-2

Cohort F: Single dose CCI15106 60 mg /Placebo

EXPERIMENTAL

Healthy subjects will receive single dose of either 60 mg CCI15106 (8 capsules of 7.5 mg) or matching placebo by inhalation via Modified Air Inlet Rotahaler™ device according to randomization.

Drug: CCI15106 7.5 mg capsule; Drug: Placebo; Drug: Placebo-2

Cohort G: CCI15106 7.5 mg /Placebo BID 14 Days

EXPERIMENTAL

Healthy subjects will receive repeat dose of either 7.5 mg CCI15106 (1 capsule) or matching placebo twice daily (BID) for 14 days by inhalation via Modified Air Inlet Rotahaler™ device according to randomization.

Drug: CCI15106 7.5 mg capsule; Drug: Placebo; Drug: Placebo-2

Cohort H: CCI15106 15 mg /Placebo BID 14 Days

EXPERIMENTAL

Healthy subjects will receive repeat dose of either 15 mg CCI15106 (2 capsules of 7.5 mg) or matching placebo BID for 14 days by inhalation via Modified Air Inlet Rotahaler™ device according to randomization.

Drug: CCI15106 7.5 mg capsule; Drug: Placebo; Drug: Placebo-2

Cohort I: CCI15106 30 mg /Placebo BID 14 Days-BAL

EXPERIMENTAL

Healthy subjects will receive repeat dose of either 30 mg CCI15106 (4 capsules of 7.5 mg) or matching placebo BID for 14 days by inhalation via Modified Air Inlet Rotahaler™ device according to randomization. BAL procedures will be performed in this cohort additionally.

Drug: CCI15106 7.5 mg capsule; Drug: Placebo; Drug: Placebo-2

Cohort J: CCI15106 =<30 mg /Placebo BID 14 Days

EXPERIMENTAL

Healthy subjects will receive repeat dose of either =\< 30 mg CCI15106 (less than or equal to 4 capsules of 7.5 mg) or matching placebo BID for 14 days by inhalation via Modified Air Inlet Rotahaler™ device according to randomization. The dose for cohort J is unknown at this time and will depend on results seen in the previous cohorts.

Drug: CCI15106 7.5 mg capsule; Drug: Placebo; Drug: Placebo-2

Cohort K: Single dose CCI15106 30 mg /Placebo-COPD

EXPERIMENTAL

COPD patients will receive single dose of either 30 mg CCI15106 (4 capsules of 7.5 mg) or matching placebo by inhalation via Modified Air Inlet Rotahaler™ device according to randomization.

Drug: CCI15106 7.5 mg capsule; Drug: Placebo; Drug: Placebo-2

Interventions

CCI15106 7.5 mg capsule DRUG

Orange capsule containing a white to off-white powder, 21.4 mg of CCI15106: Trehalose:Trileucine 35/55/10 weight by weight (w/w)

Cohort A: Single dose CCI15106 7.5 mg /Placebo; Cohort B: Single dose CCI15106 15 mg /Placebo; Cohort C: Single dose CCI15106 30 mg /Placebo; Cohort D: Single dose CCI15106 30 mg /Placebo-BAL; Cohort E: Single dose CCI15106 45 mg /Placebo; Cohort F: Single dose CCI15106 60 mg /Placebo; Cohort G: CCI15106 7.5 mg /Placebo BID 14 Days; Cohort H: CCI15106 15 mg /Placebo BID 14 Days; Cohort I: CCI15106 30 mg /Placebo BID 14 Days-BAL; Cohort J: CCI15106 =<30 mg /Placebo BID 14 Days; Cohort K: Single dose CCI15106 30 mg /Placebo-COPD

Placebo DRUG

Orange capsule containing a white to off-white powder, 21.4 mg of Trehalose:Trileucine 85/15 w/w

Cohort A: Single dose CCI15106 7.5 mg /Placebo; Cohort B: Single dose CCI15106 15 mg /Placebo; Cohort C: Single dose CCI15106 30 mg /Placebo; Cohort D: Single dose CCI15106 30 mg /Placebo-BAL; Cohort E: Single dose CCI15106 45 mg /Placebo; Cohort F: Single dose CCI15106 60 mg /Placebo; Cohort G: CCI15106 7.5 mg /Placebo BID 14 Days; Cohort H: CCI15106 15 mg /Placebo BID 14 Days; Cohort I: CCI15106 30 mg /Placebo BID 14 Days-BAL; Cohort J: CCI15106 =<30 mg /Placebo BID 14 Days; Cohort K: Single dose CCI15106 30 mg /Placebo-COPD

Placebo-2 DRUG

Orange capsule containing a white to off-white powder, 21.4 mg of lactose. Placebo-2 to be used if unexpected safety signals are observed with the use of matching placebo.

Cohort A: Single dose CCI15106 7.5 mg /Placebo; Cohort B: Single dose CCI15106 15 mg /Placebo; Cohort C: Single dose CCI15106 30 mg /Placebo; Cohort D: Single dose CCI15106 30 mg /Placebo-BAL; Cohort E: Single dose CCI15106 45 mg /Placebo; Cohort F: Single dose CCI15106 60 mg /Placebo; Cohort G: CCI15106 7.5 mg /Placebo BID 14 Days; Cohort H: CCI15106 15 mg /Placebo BID 14 Days; Cohort I: CCI15106 30 mg /Placebo BID 14 Days-BAL; Cohort J: CCI15106 =<30 mg /Placebo BID 14 Days; Cohort K: Single dose CCI15106 30 mg /Placebo-COPD

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
• Between 18 and 65 years of age inclusive, at the time of signing the informed consent.
• Healthy as determined by the investigator.
• Body weight \>= 50 kilogram (kg) for males and 45 kg for females and body mass index (BMI) within the range 19 - 31 kg/meter square (m\^2) (inclusive)
• Male or Female: Male subjects with female partners of child bearing potential must comply with the contraception requirements as specified in protocol. A female subject is eligible to participate if she is of non-reproductive potential.
• Capable of giving signed informed consent.
• For COPD Patients
• Between 40 and 75 years of age inclusive, at the time of signing the informed consent.
• Diagnosed with moderate COPD (GOLD class II) by a qualified physician as defined by the GOLD guidelines (http://www.goldcopd.org/).
• The subject has spirometry at screening, showing: a) post-bronchodilator forced expiratory volume in 1 second (FEV1)\>=50% and \<80% predicted normal; b) post-bronchodilator FEV1/ forced vital capacity (FVC)\<0.7.
• Subject is a smoker or an ex-smoker.
• Body weight \>= 45 kg and BMI within the range 17 - 32 kg/m\^2 (inclusive).
• Male or Female: Male subjects with female partners of child bearing potential must comply with the contraception requirements as specified in protocol. A female subject is eligible to participate if she is of non-reproductive potential.
• Capable of giving signed informed consent.

You may not qualify if:

• For Healthy Subjects
• Male partners of women who are pregnant or lactating
• Alanine transaminase (ALT) and/or bilirubin \>1.5xupper limit of normal (ULN) (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• QT interval corrected for heart rate (QTc )\> 450 millisecond (msec).
• Heart rate: \<40 and \>100 beats per minute (bpm) for males and \<50 and \>100 bpm for females, PR Interval: \<120 and \>220 msec, QRS duration: \<70 and \>120 msec, QTcF interval: \>450 msec
• Any clinically significant central nervous system (e.g., seizures), cardiac, pulmonary, metabolic, renal, hepatic or gastrointestinal conditions or history of such conditions.
• Unable to refrain from prescription or non-prescription drugs
• History of regular alcohol consumption within 3 months of the study
• Breath test indicative of smoking at day -1
• History of sensitivity to any of the study medications
• For cohorts that will undergo BAL, contraindications to bronchoalveolar lavage
• Documented lactose allergy/intolerance for cohorts with lactose placebo if they are used in the study.
• Hemoglobin (Hgb) below the lower level of the normal range with one repeat testing allowed, or known hemoglobinopathies.
• Known severe hypersensitivity reactions such as Stevens-Johnson Syndrome, toxic epidermal necrolysis, and erythema multiforme.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

London, NW10 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

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2017
• First Posted: August 9, 2017
• Study Start: February 10, 2016
• Primary Completion: July 20, 2016
• Study Completion: August 20, 2016
• Last Updated: June 30, 2020

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)