Study to Determine the Relative Bioavailability, Single a... | NCT04514237

ID	Type	Description	Link
2019-002289-11	EudraCT Number
QSC201870	Other Identifier	Quotient Sciences

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Part 1: Regimens AB(CD)	Experimental	Participants received 50 milligrams (mg) BOS172767 E1 tablets or matching placebo (Regimen A) in the fasted state in Period 1, followed by 50 mg BOS172767 E2 tablets or matching placebo (Regimen B) in the fasted state in Period 2. In Period 3 and 4, participants received BOS172767-Ex (selected enantiomer from Part 1 [E1 or E2]) tablets or matching placebo (Regimens C and D, respectively) from Regimen A or B in the fasted state. The Period 3 and 4 dose was selected after review of data from Periods 1 and 2. In each Period, dosing occurred on Day 1, and there was a washout period of at least 10 days or 5 half-lives of the parent (whichever is greater) between each dose of investigational medicinal product.	Drug: BOS172767 enantiomer E1 or E2 Drug: Placebo
Part 1: Regimens BA(CD)	Experimental	Participants received 50 milligrams (mg) BOS172767 E2 tablets or matching placebo (Regimen B) in the fasted state in Period 1, followed by 50 mg BOS172767 E1 tablets or matching placebo (Regimen A) in the fasted state in Period 2. In Period 3 and 4, participants received BOS172767-Ex (selected enantiomer from Part 1 [E1 or E2]) tablets or matching placebo (Regimens C and D, respectively) from Regimen A or B in the fasted state. The Period 3 and 4 dose was selected after review of data from Periods 1 and 2. In each Period, dosing occurred on Day 1, and there was a washout period of at least 10 days or 5 half-lives of the parent (whichever is greater) between each dose of investigational medicinal product.	Drug: BOS172767 enantiomer E1 or E2 Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
BOS172767 enantiomer E1 or E2	Drug	Oral tablets	Part 1: Regimens AB(CD) Part 1: Regimens BA(CD)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Part 1: Relative bioavailability of E1 versus E2 (Frel; exposure) of a single oral dose of BOS172767 enantiomer 1 (E1) and enantiomer 2 (E2) following administration to healthy participants based on Cmax, AUC(0-last), and AUC (0-inf)	Cmax is defined as the maximum observed concentration. AUC(0-last) is defined as the area under the curve from 0 time to the last measurable concentration. AUC (0-inf) is defined as the area under the curve from 0 time extrapolated to infinity.	24 hours post-dose for each of the four 6-day Periods
Part 1: Number of participants with any treatment-emergent adverse event		up to Day 6 of each Period; up to a 10-day Follow-up Period after last dose (up to Study Day 59)
Part 1: Number of participants with abnormal, clinically significant physical examination findings		up to Day 6 of each Period; up to a 10-day Follow-up Period after last dose (up to Study Day 59)
Part 1: Number of participants with abnormal, clinically significant safety laboratory test findings		up to Day 6 of each Period; up to a 10-day Follow-up Period after last dose (up to Study Day 59)
Part 1: Number of participants with abnormal, clinically significant vital sign values		up to Day 6 of each Period; up to a 10-day Follow-up Period after last dose (up to Study Day 59)
Part 1: Number of participants with abnormal, clinically significant electrocardiogram findings		up to Day 6 of each Period; up to a 10-day Follow-up Period after last dose (up to Study Day 59)
Part 1: Plasma concentration of BOS172767 enantiomers 1 and 2

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Healthy males or healthy females of non-childbearing potential
Age 18 to 50 years at the time of signing informed consent
Body mass index (BMI) of 18.0 to 32.0 kilograms per meters squared (kg/m^2) as measured at screening
Must have been willing and able to communicate and participate in the whole study
Must have provided written informed consent
Must have agreed to adhere to the contraception requirements for this study

Exclusion Criteria:

Participants who received any investigational medicinal product (IMP) in a clinical research study within the 90 days prior to Day 1
Participants who were study site employees, or immediate family members of a study site or sponsor employee
Participants who had previously been enrolled and dosed in this study. Participants who had taken part in Part 1 were not permitted to take part in Part 2. Participants who had taken part in study QCL118174/BOS172767-01 (NCT03464058) were allowed to participate in this study.
History of any drug or alcohol abuse in the past 2 years
Regular alcohol consumption in males >21 units per week and females >14 units per week (1 unit = 1/2 pint beer, or a 25 milliliter [mL] shot of 40% spirit, 1.5 to 2 Units = 125 mL glass of wine, depending on type)
A confirmed positive alcohol breath test at screening or admission
Current smokers and those who had smoked within the last 6 months. A confirmed breath carbon monoxide reading of greater than 20 parts per million (ppm) at screening or admission.
Current users of e-cigarettes and nicotine replacement products and those who had used these products within the last 6 months
Females of childbearing potential including those who were pregnant or lactating (all female participants must have had a negative serum pregnancy test at screening and had a negative urine pregnancy test at all other time points). A woman was considered of childbearing potential unless she was permanently sterile (hysterectomy, bilateral salpingectomy, and bilateral oophorectomy) or was postmenopausal (had no menses for 12 months without an alternative medical cause and a serum follicle-stimulating hormone [FSH] concentration ≥40 International Units per Liter [IU/L])
Participants who did not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator or delegate at screening
Clinically significant abnormal clinical chemistry, haematology, or urinalysis as judged by the investigator. Participants with Gilbert's Syndrome were not allowed.
Participants with alanine aminotransferase (ALT) > 1.5 x upper limit of normal (ULN) at screening (Part 1 and Part 2) or Day -1 (Part 2 only)
Confirmed positive drugs of abuse test result
Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab), or human immunodeficiency virus (HIV) results
Evidence of renal impairment at screening, as indicated by an estimated creatinine clearance (CLcr) of <70 milliliters per minute (mL/min) using the Cockcroft-Gault equation
History of clinically significant cardiovascular, renal, hepatic, chronic respiratory, or gastrointestinal disease (including gall stones and/or cholecystectomy), or neurological or psychiatric disorder, as judged by the investigator
Serious adverse reaction or serious hypersensitivity to any drug or the IMP excipients
Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever was allowed unless it was active.
Donation or loss of greater than 400 mL of blood within the previous 3 months
Participants who were taking, or had taken, any prescribed or over-the-counter drug (other than 4 grams of paracetamol per day and/or hormone replacement therapy [HRT]) or herbal remedies in the 14 days before IMP administration. Exceptions may have applied on a case by case basis, if considered not to have interfered with the objectives of the study, as determined by the principal investigator.
Participants who had any ongoing fungal infections (stable toe nail onchomycosis was allowed)
Failure to satisfy the investigator of fitness to participate for any other reason