A Phase 1 Bioavailability Study of Arbaclofen Placarbil Modified Release Formulations in Healthy Volunteers

• Status: Completed
• Trial end date: 2017-07-05
• Target enrollment: 0
• Participant gender: All

Summary

Part 1

• To evaluate the pharmacokinetic (PK) profile of Arbaclofen Placarbil (AP) and R-baclofen following dosing of Arbaclofen Placarbil Modified Release (MR) Prototype A Tablet and Arbaclofen Placarbil MR Prototype B Tablet in healthy subjects

• To determine the relative bioavailability of AP and R-baclofen following dosing of Arbaclofen Placarbil MR Prototype A Tablet and Arbaclofen Placarbil MR Prototype B Tablet compared to the reference Arbaclofen Placarbil Sustained Release (SR) Tablets (low dose)

• To determine the relative bioavailability and PK of AP and R-baclofen following dosing of the selected MR prototype formulation(s) in the presence of beverage

• To provide additional information on the safety and tolerability of single doses of AP

Part 2

• To evaluate the PK profile of AP and R-baclofen following dosing of Arbaclofen Placarbil MR Prototype Tablets in healthy subjects

• To determine the relative bioavailability and PK of AP and R-baclofen following dosing of Arbaclofen Placarbil MR Prototype Tablets compared to the reference Arbaclofen Placarbil Immediate Release (IR) Capsule

• To provide additional information on the safety and tolerability of single doses of AP

• To determine the relative bioavailability and PK of AP and R-baclofen following dosing of a selected MR prototype formulation in the fed state (optional)

• To explore a possible in vitro in vivo correlation/relationship (IVIVC/IVIVR) for the Arbaclofen Placarbil MR Prototype Tablet Formulations

Part 3

• To determine the relative bioavailability of the selected Arbaclofen Placarbil MR Prototype Tablet in the presence of either beverage or food and/or

• To evaluate the PK profile (dose proportionality) of AP and R-baclofen following dosing of the selected Arbaclofen Placarbil MR Prototype A + B Tablet at different dose levels in healthy subjects

• To provide additional information on the safety and tolerability of single doses of AP

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Indivior Inc.
• Treatments: Arbaclofen placarbil; Baclofen

Criteria

Inclusion Criteria:

• Healthy males

• Non-pregnant, non-lactating healthy females

• Body mass index of 18.0 to 30.0 kg/m^2 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 provide written informed consent prior to any study-specific procedures

• Must agree to use an adequate method of contraception

Exclusion Criteria:

• Subjects who have received any IMP in a clinical research study within the previous 3 months

• Subjects who are study site employees, or immediate family members of a study site or sponsor employee

• Subjects who have previously been enrolled in this study

• History of any clinically significant drug/substance or alcohol abuse or disorders in the past 2 years

• Regular alcohol consumption in males >21 units per week and females >14 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine)

• Regular alcohol consumption <5 units per week on average

• Current smokers and those who have smoked within the last 12 months. A breath carbon monoxide reading of greater than 10 ppm at screening and each admission

• Current smokers of e-cigarettes and nicotine replacement products and those who have smoked these products within the last 12 months

• Females of childbearing potential who are pregnant or lactating (female subjects must have a negative urine pregnancy test). A woman is considered of childbearing potential unless she is permanently sterile (hysterectomy, bilateral salpingectomy or bilateral oophorectomy) or is postmenopausal (had no menses for 12 months without an alternative medical cause and a serum follicle-stimulating hormone [FSH] concentration ≥40 IU/L)

• Subjects 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

• Clinically significant abnormal ECG as judged by the investigator, including a QT interval corrected using Fridericia's formula of >450 msec in males and >470 msec in females

• Positive drugs of abuse test result at screening and each admission (drugs of abuse tests are listed in the protocol)

• 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 of <70 mL/min using the Cockcroft-Gault equation

• History of cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease or psychiatric disorder, as judged by the investigator

• History of surgical procedures involving the brain or meninges, encephalitis, meningitis, degenerative central nervous system disorder (eg, Alzheimer's or Parkinson's Disease), epilepsy, mental retardation, or any other disease/procedure/accident/intervention associated with significant injury to or malfunction of the central nervous system, or a history of significant head trauma within the past 2 years, or currently receiving anticonvulsant therapy for any reason

• Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients

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

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

• Subjects who are taking, or have taken, any prescribed or over-the-counter drug (other than 4 g per day paracetamol, hormone replacement therapy and hormonal contraceptives) 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 PI and sponsor's medical monitor.

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