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

Healthy Subjects Clinical Trial

Official title:

A Phase 1 Study to Determine the Single and Repeat Dose Pharmacokinetics, Food Effect, PPI Drug Interaction, Safety and Tolerability of Oral Prototype Formulations of BOS172767 in Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03464058
• Other study ID #: BOS172767-01
• Secondary ID: 2017-004002-18QC
• Status: Completed
• Phase: Phase 1
• Start date: March 21, 2018
• Est. completion date: October 10, 2018

Study information

• Verified date: November 2020
• Source: Boston Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Part 1 is comprised of a single-dose, part-randomized, open-label, 6-way crossover in 12 healthy participants. Participants will be dosed on 6 separate occasions (in 6 treatment periods), and will receive a single prototype of BOS172767 in each treatment period.

Part 2 is comprised of a single ascending dose, fixed-sequence, open-label, 3-way crossover with an optional fourth dosing period in 10 healthy participants. Participants will be dosed on 4 separate occasions (in 4 treatment periods), and will receive a single prototype of BOS172767 in each treatment period.

Part 3 is a double-blind (sponsor-open), placebo-controlled, randomized MAD part in 36 healthy participants (12 per study cohort). Participants will be dosed on 3 separate occasions (in 3 treatment periods), and will receive a single prototype of BOS172767 in each treatment period.

Parts 2 and 3 are contingent upon successful completion of Part 1.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: October 10, 2018
• Est. primary completion date: October 9, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

• Adverse reaction to rabeprazole, its excipients or any proton pump inhibitors (Part 2 only)

• Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever is allowed unless it is active.

• Donation or loss of greater than 400 mL of blood within the previous 3 months

• Participants who are taking, or have taken, any prescribed or over-the-counter drug (other than 4 grams per day paracetamol or hormone replacement therapy) or herbal remedies in the 14 days before IMP administration. Exceptions may apply on a case by case basis, if considered not to interfere with the objectives of the study, as agreed by the Principal Investigator and sponsor's medical monitor.

• Participants who have any ongoing fungal infections (stable toe nail onychomycosis is allowed)

• Failure to satisfy the investigator of fitness to participate for any other reason

Related Conditions & MeSH terms

• Healthy Subjects

Intervention

Drug:
• BOS172767 tablets
Oral tablets
• BOS172767 liquid capsules
Oral capsules
• BOS172767 micronized capsules
Oral capsules
• BOS172767 immediate release capsules
Oral capsules
• BOS172767 matching placebo capsules
Oral capsules
• BOS172767 matching placebo tablets
Oral tablets
• Rabeprazole
Oral tablets

Locations

Country	Name	City	State
United Kingdom	Quotient Sciences	Nottingham

Sponsors (1)

Lead Sponsor	Collaborator
Boston Pharmaceuticals

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Parts 1, 2, and 3: Number of participants with any treatment-emergent serious adverse event (TESAE)		up to 33 weeks
Primary	Parts 1, 2, and 3: Number of participants with any treatment-emergent non-serious adverse event (TEAE)		up to 33 weeks
Primary	Parts 1, 2, and 3: Number of participants with abnormal, clinically significant physical examination findings		up to 33 weeks
Primary	Parts 1, 2, and 3: Number of participants with abnormal, clinically significant safety laboratory test findings		up to 33 weeks
Primary	Parts 1, 2, and 3: Number of participants with abnormal, clinically significant vital sign values		up to 33 weeks
Primary	Parts 1, 2, and 3: Number of participants with abnormal, clinically significant electrocardiogram findings		up to 33 weeks
Primary	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)
Primary	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
Primary	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
Primary	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