Study to Determine the Single and Repeat Dose Pharmacokinetics, Food Effect, Proton Pump Inhibitor (PPI) Drug Interaction, Safety and Tolerability of Oral Prototype Formulations of BOS172767 in Healthy Subjects

NCT03464058 | Completed Phase 1 FDA Drug

• 3 other identifiers: BOS172767-012017-004002-18QCL118174
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

Part 1 of the study will be conducted to provide additional information on the safety and tolerability of single doses of BOS172767 in healthy participants, to evaluate the pharmacokinetic (PK) profiles (including relative bioavailability) of BOS172767 following oral administration of 3 prototype formulations in healthy participants compared to an immediate release capsule formulation (reference), and also to determine the relative bioavailability of a selected BOS172767 prototype formulation in the fed and fasted states. Part 2 of the study will be conducted to provide additional information on the safety and tolerability of escalating single doses of the selected formulation of BOS172767 in healthy participants, to evaluate the PK profile following increased single doses of the selected formulation of BOS172767 following administration in healthy participants, and also to evaluate the dose linearity of the selected prototype. Part 3 of the study will be conducted to provide additional information on the safety, tolerability, and PK of the selected formulation of BOS172767 following multiple ascending doses (MADs) over 14 days of dosing in healthy participants.

Conditions

Healthy Subjects

Keywords

Pharmacokinetics; Food Effect; Proton Pump Inhibitors; Drug Interaction; Oral Prototype Formulations

Outcome Measures

Primary Outcomes (10)

• Parts 1, 2, and 3: Number of participants with any treatment-emergent serious adverse event (TESAE)

  up to 33 weeks

• Parts 1, 2, and 3: Number of participants with any treatment-emergent non-serious adverse event (TEAE)

  up to 33 weeks

• Parts 1, 2, and 3: Number of participants with abnormal, clinically significant physical examination findings

  up to 33 weeks

• Parts 1, 2, and 3: Number of participants with abnormal, clinically significant safety laboratory test findings

  up to 33 weeks

• Parts 1, 2, and 3: Number of participants with abnormal, clinically significant vital sign values

  up to 33 weeks

• Parts 1, 2, and 3: Number of participants with abnormal, clinically significant electrocardiogram findings

  up to 33 weeks

• Parts 1 and 2: Plasma concentration of BOS172722

  predose; 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16 hours postdose (Day 1); 24 and 36 hours postdose (Day 2); 48 hours postdose (Day 3)

• Part 2 (Regimen I): Plasma concentration of BOS172722

  admission to pre-dose (admission to dosing), 0 to 6 (Day 1), 6 to 12 (Day 1), 12 to 24 (Day 1), and 24 to 48 (Days 2 to 3) hours postdose

• Part 3: Plasma concentration of BOS172722

  Days 1 and 7: pre-dose; 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours postdose. Days 4, 6, 9, 11, and 12: pre-dose. Day 14: pre-dose; 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, and 120 hours post-final dose

• Part 3 (Regimen M): Plasma concentration of BOS172722

  admission to pre-dose on Day 1; 0 to 6, 6 to 12, and 12 to 24 hours postdose on Days 1, 7, and 14

Study Arms (13)

Part 1: Regimen A

EXPERIMENTAL

Participants will be treated with a BOS172767 200 milligram (mg) spray dried dispersion tablet (2 × 100 mg tablets) in the fasted state on Day 1.

Drug: BOS172767 tablets

Part 1: Regimen B

EXPERIMENTAL

Participants will be treated with a BOS172767 200 mg lipid capsule (2 × 100 mg capsules) in the fasted state on Day 1.

Drug: BOS172767 liquid capsules

Part 1: Regimen C

EXPERIMENTAL

Participants will be treated with a BOS172767 200 mg micronized capsule (2 × 100 mg capsules) in the fasted state on Day 1.

Drug: BOS172767 micronized capsules

Part 1: Regimen D

EXPERIMENTAL

Participants will be treated with a BOS172767 200 mg immediate release reference capsule formulation (2 × 100 mg capsules) in the fasted state on Day 1.

Drug: BOS172767 immediate release capsules

Part 1: Regimen E

EXPERIMENTAL

Participants will be treated with a selected dose of a prototype formulation of BOS172767 in the fasted state on Day 1.

Drug: BOS172767 tablets; Drug: BOS172767 liquid capsules; Drug: BOS172767 micronized capsules; Drug: BOS172767 immediate release capsules

Part 1: Regimen F

EXPERIMENTAL

Participants will be treated with a selected dose of a prototype formulation of BOS172767 in the fed state on Day 1.

Drug: BOS172767 tablets; Drug: BOS172767 liquid capsules; Drug: BOS172767 micronized capsules; Drug: BOS172767 immediate release capsules

Part 2: Regimen G

EXPERIMENTAL

Participants will be treated with 400 mg of the selected BOS172767 prototype in the fasted state on Day 1.

Drug: BOS172767 tablets; Drug: BOS172767 liquid capsules; Drug: BOS172767 micronized capsules; Drug: BOS172767 immediate release capsules

Part 2: Regimen H

EXPERIMENTAL

Participants will be treated with 600 mg of the selected BOS172767 prototype in the fasted state on Day 1.

Drug: BOS172767 tablets; Drug: BOS172767 liquid capsules; Drug: BOS172767 micronized capsules; Drug: BOS172767 immediate release capsules

Part 2: Regimen I

EXPERIMENTAL

Participants will be treated with 800 mg of the selected BOS172767 prototype in the fasted state on Day 1.

Drug: BOS172767 tablets; Drug: BOS172767 liquid capsules; Drug: BOS172767 micronized capsules; Drug: BOS172767 immediate release capsules

Part 2: Regimen J

EXPERIMENTAL

Participants will be treated with rabeprazole on Days -3 to -1, and a selected dose of the BOS172767 prototype in the fasted state on Day 1.

Drug: BOS172767 tablets; Drug: BOS172767 liquid capsules; Drug: BOS172767 micronized capsules; Drug: BOS172767 immediate release capsules; Drug: Rabeprazole

Part 3: Regimen K

EXPERIMENTAL

Participants will be treated with 400 mg of a BOS172767 prototype or matching placebo once daily (QD) or twice daily (BID) for 14 days (Days 1 to 14).

Drug: BOS172767 tablets; Drug: BOS172767 liquid capsules; Drug: BOS172767 micronized capsules; Drug: BOS172767 immediate release capsules; Drug: BOS172767 matching placebo capsules; Drug: BOS172767 matching placebo tablets

Part 3: Regimen L

EXPERIMENTAL

Participants will be treated with 600 mg of a BOS172767 prototype or matching placebo QD or BID for 14 days (Days 1 to 14).

Drug: BOS172767 tablets; Drug: BOS172767 liquid capsules; Drug: BOS172767 micronized capsules; Drug: BOS172767 immediate release capsules; Drug: BOS172767 matching placebo capsules; Drug: BOS172767 matching placebo tablets

Part 3: Regimen M

EXPERIMENTAL

Participants will be treated with 800 mg of a BOS172767 prototype or matching placebo QD or BID for 14 days (Days 1 to 14).

Drug: BOS172767 tablets; Drug: BOS172767 liquid capsules; Drug: BOS172767 micronized capsules; Drug: BOS172767 immediate release capsules; Drug: BOS172767 matching placebo capsules; Drug: BOS172767 matching placebo tablets

Interventions

BOS172767 tablets DRUG

Oral tablets

Part 1: Regimen A; Part 1: Regimen E; Part 1: Regimen F; Part 2: Regimen G; Part 2: Regimen H; Part 2: Regimen I; Part 2: Regimen J; Part 3: Regimen K; Part 3: Regimen L; Part 3: Regimen M

BOS172767 liquid capsules DRUG

Oral capsules

Part 1: Regimen B; Part 1: Regimen E; Part 1: Regimen F; Part 2: Regimen G; Part 2: Regimen H; Part 2: Regimen I; Part 2: Regimen J; Part 3: Regimen K; Part 3: Regimen L; Part 3: Regimen M

BOS172767 micronized capsules DRUG

Oral capsules

Part 1: Regimen C; Part 1: Regimen E; Part 1: Regimen F; Part 2: Regimen G; Part 2: Regimen H; Part 2: Regimen I; Part 2: Regimen J; Part 3: Regimen K; Part 3: Regimen L; Part 3: Regimen M

BOS172767 immediate release capsules DRUG

Oral capsules

Part 1: Regimen D; Part 1: Regimen E; Part 1: Regimen F; Part 2: Regimen G; Part 2: Regimen H; Part 2: Regimen I; Part 2: Regimen J; Part 3: Regimen K; Part 3: Regimen L; Part 3: Regimen M

BOS172767 matching placebo capsules DRUG

Oral capsules

Part 3: Regimen K; Part 3: Regimen L; Part 3: Regimen M

BOS172767 matching placebo tablets DRUG

Oral tablets

Part 3: Regimen K; Part 3: Regimen L; Part 3: Regimen M

Rabeprazole DRUG

Oral tablets

Part 2: Regimen J

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy males or healthy females of non-child bearing potential
• Age 18 to 50 years of age at time of signing informed consent
• Body mass index of 18.0 to 32.0 kilograms per meters squared (kg/m\^2) at Screening, or, if outside the range, considered not clinically significant by the investigator
• Must be willing and able to communicate and participate in the whole study
• Must have a negative Quantiferon tuberculosis test at Screening
• Must provide written informed consent
• Must agree to use an adequate method of contraception

You may not qualify if:

• Participants who have received any investigational medicinal product (IMP) in a clinical research study within the previous 3 months prior to dosing
• Participants who are study site employees, or immediate family members of a study site or sponsor employee
• Participants who have previously been enrolled (dosed) in this study
• History of any drug or alcohol abuse in the past 2 years prior to Screening
• Regular alcohol consumption in males \>21 units per week and females \>14 units per week (1 unit = ½ pint beer, 25 milliliters \[mL\] of 40% spirit or a 125 mL glass of wine)
• Current smokers and those who have smoked within the last 12 months prior to Screening. A breath carbon monoxide reading of greater than 20 parts per million at Screening or admission
• Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months prior to Screening
• Females of childbearing potential
• Participants who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator at Screening
• Clinically significant abnormal biochemistry, haematology or urinalysis as judged by the investigator
• Confirmed positive drugs of abuse test result
• Positive hepatitis B surface antigen, hepatitis C virus antibody or human immunodeficiency virus results
• Evidence of renal impairment at Screening, as indicated by an estimated creatinine clearance of \<70 mL/minute using the Cockcroft-Gault equation
• History of clinically significant cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease (including gall stones and/or cholecystectomy), neurological or psychiatric disorder, as judged by the investigator
• Serious adverse reaction or serious hypersensitivity to any drug or the IMP formulation excipients

Sponsors & Collaborators

• Boston Pharmaceuticals: lead

Study Sites (1)

Quotient Sciences

Nottingham, United Kingdom

Location

MeSH Terms

Interventions

Rabeprazole

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Part 1 and 2 of the study are open-label and therefore blinding is not required. Part 3 of the study is double-blind.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 7, 2018
• First Posted: March 13, 2018
• Study Start: March 21, 2018
• Primary Completion: October 9, 2018
• Study Completion: October 10, 2018
• Last Updated: November 18, 2020

Record last verified: 2020-11

Locations

GB (1)