GSK1325756 Relative Bioavailability Study in Healthy Elderly Subjects

NCT03457727 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 207573
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This 2-part study will be carried out on healthy elderly subjects to evaluate relative bioavailability of danirixin formulations. Part A will support the selection of the formulation and Part B will assess food effect, bioavailability and pharmacokinetic (PK) profile of selected formulation from Part A. Danirixin is currently administered with food, therefore the investigation of food effect for the selected formulation could potentially enable dosing without food. Approximately 16 subjects will be included in Part A and approximately 24 subjects will be included in Part B. Both parts will include a screening phase, treatment phase with in-between washout period and a follow-up phase.

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

Danirixin; Healthy; Food effect; Relative Bioavailability; Hydrobromide Salt

Outcome Measures

Primary Outcomes (6)

• Area Under the Concentration-time Curve From Time 0 to Infinity (AUC [0-inf]) of Danirixin for Part 1

  Blood samples were collected at the indicated time points after administration of study treatment to investigate the pharmacokinetic (PK) profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.

  Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1

• Maximum Observed Concentration (Cmax) of Danirixin for Part 1

  Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.

  Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1

• Number of Participants With Any Adverse Event (AE) and Serious Adverse Events (SAEs) in Part 1

  AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is 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, or is a congenital anomaly/birth defect or is medically significant.

  Up to 29 days in Part 1

• Number of Participants With Vital Signs of Potential Clinical Concern in Part 1

  Vital signs included systolic and diastolic blood pressure, temperature, respiratory rate and pulse rate were measured with participants in semi-supine position after 5 minutes rest.

  Up to 29 days in Part 1

• Number of Participants With 12-lead Electrocardiogram (ECG) Values of Potential Clinical Concern in Part 1

  Single 12-lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, and QT intervals, and QT interval corrected by Fridericia's formula (QTcF). Number of participants with 12-lead ECG values of potential clinical concern in Part 1 are presented.

  Up to 29 days in Part 1

• Number of Participants With Laboratory Values of Potential Clinical Concern in Part 1

  Hematology parameters included platelet count, RBC Count, hemoglobin, hematocrit, MCV, MCH, %Reticulocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils. Clinical chemistry parameters included potassium aspartate aminotransferase(AST)/Serum Glutamic-Oxaloacetic Transaminase (SGOT), total and direct bilirubin, creatinine, sodium alanine, aminotransferase, (ALT)/ Serum Glutamic-Pyruvic, Transaminase (SGPT), total protein, fasting glucose, calcium, alkaline phosphatase and albumin. Urinalysis included specific gravity, potential of hydrogen (pH), glucose, protein, blood and ketones by dipstick and microscopic examination of urine.

  Up to 29 days in Part 1

Secondary Outcomes (18)

• Area Under the Concentration-time Curve From Time 0 to t (AUC [0-t]) of Danirixin for Part 1

  Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1

• Area Under the Concentration-time Curve From Time 0 to 24 Hours Post-dose (AUC [0-24]) of Danirixin for Part 1

  Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1

• Time to Occurrence of Cmax (Tmax) of Danirixin for Part 1

  Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1

• Terminal Half-life (t1/2) of Danirixin for Part 1

  Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1

• Time to Last Quantifiable Concentration (Tlast) of the Blood Concentration of Danirixin for Part 1

  Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1

Study Arms (3)

Subjects receiving danirixin: Part A

EXPERIMENTAL

Subjects will receive a single oral dose of 50 mg danirixin reference and test formulations with food and 240 mL of water in a cross-over manner.

Drug: Danirixin

Subjects receiving danirixin without omeprazole: Part B

EXPERIMENTAL

Subjects will receive a single oral dose of 50 mg danirixin formulation (selected in Part A) in fasted or fed state in a cross-over manner.

Drug: Danirixin

Subjects receiving danirixin with omeprazole: Part B

EXPERIMENTAL

Subjects will receive a single oral dose of 50 mg danirixin formulation (selected in Part A) along with once daily 40 mg OMP capsule in fasted or fed state in a cross-over manner.

Drug: Danirixin; Drug: Omeprazole

Interventions

Danirixin DRUG

Danirixin is being developed as a potential anti-inflammatory agent for the treatment of chronic obstructive pulmonary disorder (COPD) and other inflammatory diseases and influenza. Danirixin reference (600 mg) or test formulation (475 or 600 mg or 600 mg with 5 percent HPMC) immediate release tablets will be administered by oral route in a cross-over manner.

Subjects receiving danirixin with omeprazole: Part B; Subjects receiving danirixin without omeprazole: Part B; Subjects receiving danirixin: Part A

Omeprazole DRUG

Omeprazole is used as an antacid. OMP 40 mg delayed-release capsule will be administered by oral route to randomized subjects.

Subjects receiving danirixin with omeprazole: Part B

Eligibility Criteria

• Age: 65 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• Subjects must be 65 to 80 years of age inclusive, at the Screening Visit.

You may not qualify if:

• Body weight \>=50 kilograms (kg) and body mass index (BMI) within the range 19 - 34 kg per meter square (kg/m\^2) (inclusive).
• Male or female subjects will be included. A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential (WOCBP) or a WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 60 hours after the last dose of study treatment.
• Capable of giving signed informed consent.
• AST, ALT, alkaline phosphatase and bilirubin \<= 1.5 × upper limit of normal (ULN) (isolated bilirubin \> 1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin \< 35 percent).
• Resting BP of \<= 160/90 millimeters of mercury (mmHg), irrespective of anti-hypertensive medication status for the subject.
• Able to consume the Food and Drug Administration (FDA) defined high fat meal within 30 minutes in each of the four treatment periods where study treatment is administered in a fed state.
• Significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data.
• Evidence of active or latent tuberculosis (TB) as documented by medical history and examination, chest x-rays (posterior anterior and lateral), and TB testing: either a positive tuberculin skin test \[TST; defined as a skin induration \<5 millimeter (mm) at 48 to 72 hours, regardless of Bacillus Calmette-Guerin (BCG) or other vaccination history\] or a positive (not indeterminate) QuantiFERON®-TB Gold test.
• Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
• Breast cancer within the past 10 years.
• ALT \>1.5x ULN
• Bilirubin \>1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35 percent).
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• Corrected QT interval (QTc) \>450 milliseconds (msec).
• Use of prescription or non-prescription drugs, including proton pump inhibitors, histamine receptor 2 antagonists, systemic antacid medications (unless these can be held during the study), vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study treatment until completion of the last study assessment , unless in the opinion of the investigator and GSK Medical Monitor, the medication will not interfere with the study procedures or compromise subject safety. Some examples of exceptions (permitted medications) are: Stable dose of anti-hypertensive medication for at least 3 months prior to the screening visit; Stable dose of lipid-lowering medications (statins or fibrates) for at least 3 months prior to the screening visit; Antacids up to 24 hours prior to dosing.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Overland Park, Kansas, 66211, United States

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

danirixin; Omeprazole

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

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: NONE
• Masking Details: This will be an open-label study and blinding will not be performed.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Subjects will receive danirixin reference and test formulations in a cross-over manner.

Study Record Dates

• First Submitted: March 1, 2018
• First Posted: March 7, 2018
• Study Start: March 7, 2018
• Primary Completion: July 25, 2018
• Study Completion: July 25, 2018
• Last Updated: May 19, 2021
• Results First Posted: August 28, 2019

Record last verified: 2021-04

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 (copy the URL below to your browser)
• 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

US (1)