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Arbaclofen Placarbil

Phase 2

Alcohol Use Disorder | Small molecule | Psychiatry |Indivior Pharmaceuticals, Inc.|Last Updated: Jan 17, 2018

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLEDDMCBiomarker
Total Trials1
Total Enrollment18

FDA Designations

No designations recorded

Clinical trial landscape

Arbaclofen Placarbil · 2 trials · 2 indications

Phase 2 1Phase 1 1
NCT02511886A Dose-Escalation Study to Determine the Maximum Tolerated Dose of Arbaclofen Placarbil in Subjects With Alcohol Use DisorderAlcohol Use Disorder
COMPLETED18 Analytics
PHASE2COMPLETED
A Dose-Escalation Study to Determine the Maximum Tolerated Dose of Arbaclofen Placarbil in Subjects With Alcohol Use Disorder
Alcohol Use DisorderUnlock trial analytics

Study Endpoints

Primary Endpoints

Maximum Tolerated Dose (MTD) of Arbaclofen Placarbil
Up to 30 day residential (inpatient) treatment period

A data monitoring committee (DMC) will review and make a recommendation to stop dosing escalation based on the review of the unblinded AE and safety assessments or when at least one subject on active investigational product experiences an SAE related to the investigational product. The MTD and the dosage that will not be exceeded in the further development of this compound will be based upon a comprehensive review of the safety data.

Maximum Observed Plasma Concentration of Arbaclofen Placarbil (AP) (Cmax)
Prior to the initial dose of AP on day 1 and 0.5, 1, 2, 3, 4, 5, 6, 7, 8,10, 12, 16, 20, and 24 hours post-dose (predose day 2); and prior to dose of AP on days 6, 12, 18, and 24 and 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 hours post dose

Blood samples will be obtained and plasma concentrations determined using a validated liquid chromatography with tandem mass spectrometry methods

Time to Maximum Observed Plasma Concentration of Arbaclofen Placarbil (AP) (Tmax)
Prior to the initial dose of AP on day 1 and 0.5, 1, 2, 3, 4, 5, 6, 7, 8,10, 12, 16, 20, and 24 hours post-dose (predose day 2); and prior to dose of AP on days 6, 12, 18, and 24 and 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 hours post dose

Blood samples will be obtained and plasma concentrations determined using a validated liquid chromatography with tandem mass spectrometry methods

Area Under the Concentration -Time Curve from time 0 to the time of the last quantifiable plasma concentration (AUClast)
Prior to the initial dose of AP on day 1 and 0.5, 1, 2, 3, 4, 5, 6, 7, 8,10, 12, 16, 20 hours post dose

Blood samples will be obtained and plasma concentrations determined using a validated liquid chromatography with tandem mass spectrometry methods

Area Under the Concentration -Time Curve from time 0 extrapolated to infinite time (AUCinf)
Prior to the initial dose of AP on day 1 and 0.5, 1, 2, 3, 4, 5, 6, 7, 8,10, 12, 16, 20 hours post dose

Blood samples will be obtained and plasma concentrations determined using a validated liquid chromatography with tandem mass spectrometry methods

Area Under the Concentration -Time Curve from time 0 to 12 hours post dose(AUC0-12)
Prior to the initial dose of AP on day 1 and 0.5, 1, 2, 3, 4, 5, 6, 7, 8,10, 12, 16, 20 hours post dose

Blood samples will be obtained and plasma concentrations determined using a validated liquid chromatography with tandem mass spectrometry methods

Apparent Terminal Plasma Half-Life (t 1/2)
Prior to the initial dose of AP on day 1 and 0.5, 1, 2, 3, 4, 5, 6, 7, 8,10, 12, 16, 20 hours post

Blood samples will be obtained and plasma concentrations determined using a validated liquid chromatography with tandem mass spectrometry methods

Apparent Terminal Phase Rate Constant
Prior to the initial dose of AP on day 1 and 0.5, 1, 2, 3, 4, 5, 6, 7, 8,10, 12, 16, 20 hours post dose

Apparent terminal rate constant (1/h), determined by linear regression of the terminal points of the log-linear concentration-time curve. Visual assessment will be used to identify the terminal linear phase of the concentration-time profile. A minimum of 3 data points will be used for determination.

Percentage of AUCinf obtained by extrapolation (%AUCex)
Prior to the initial dose of AP on day 1 and 0.5, 1, 2, 3, 4, 5, 6, 7, 8,10, 12, 16, 20 hours post dose

If the extrapolated area is greater than 20% of AUCinf, then AUCinf will be listed but not included in summary presentations or statistical analyses

Apparent Oral Clearance (CL/F)
Prior to the initial dose of AP on day 1, 6, 12, 18, 24 and 0.5, 1, 2, 3, 4, 5, 6, 7, 8,10, 12, 16, 20 hours post dose

Calculated as Dose/AUCinf

Apparent Volume of Distribution (Vz/F)
Prior to the initial dose of AP on day 1 and 0.5, 1, 2, 3, 4, 5, 6, 7, 8,10, 12, 16, 20 hours post dose

Calculated as Dose/apparent terminal phase rate constant \* AUCinf

Area Under the Plasma Concentration-Time Curve From Time Zero To The End of Dosing Interval (AUCtau)
Prior to dose of AP on days 6, 12, 18, and 24 and 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 hours post dose

Area Under the Plasma Concentration-Time Curve From Time 0 to the End of the Dosing Interval

Minimum Observed Plasma Concentration (Cmin)
Prior to dose of AP on days 6, 12, 18, and 24 and 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 hours post dose

Blood samples will be obtained and plasma concentrations determined using a validated liquid chromatography with tandem mass spectrometry methods

Pre-Dose Plasma Concentration (Ctrough)
Prior to dose of AP on days 6, 12, 18, 19, 20, 21, 22, 23, and 24 hours post dose

Blood samples will be obtained and plasma concentrations determined using a validated liquid chromatography with tandem mass spectrometry methods

Part 1: Time to Maximum Concentration (Tmax) of Arbaclofen Placarbil (AP) and R-baclofen in Low Dose Arbaclofen Placarbil Modified Release (MR) Prototypes A + B
Day 1 (pre-dose), post-dose up to 48 hours

Part of the pharmacokinetic profile of arbaclofen placarbil (AP) and R-baclofen in low dose arbaclofen placarbil modified release (MR) prototypes A and B.

Secondary Endpoints

The Number of Participants Who Experienced Serious or Non-Serious Adverse Events
Up to 11 weeks
Columbia Suicide Severity Rating Scale (C-SSRS)
Up to 11 weeks
The Obsessive-Compulsive Drinking Scale (OCDS)
Up to 11 weeks
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Study Design & Arms

AllocationRANDOMIZED
MaskingDOUBLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Arbaclofen Placarbil (AP)EXPERIMENTALOrally administered Arbaclofen Placarbil (AP) sustained release (SR) tablets
PlaceboPLACEBO_COMPARATORSubjects remain on placebo for entire study
Part 1: Regimen AEXPERIMENTALOne low dose Arbaclofen Placarbil MR Prototype A tablet taken under fasting conditions. Part 1 participants receive Regimens A, B, C, D and E in a sequential manner.
Part 1: Regimen BEXPERIMENTALOne low dose Arbaclofen Placarbil MR Prototype B tablet taken under fasting conditions. Part 1 participants receive Regimens A, B, C, D and E in a sequential manner.
Part 1: Regimen CACTIVE_COMPARATOROne low dose Arbaclofen Placarbil SR tablet taken under fasting conditions as the reference product. Part 1 participants receive Regimens A, B, C, D and E in a sequential manner.
Part 1: Regimen DEXPERIMENTALOne low dose tablet of the selected Arbaclofen Placarbil MR Prototype administered with 0.6 g/kg of beverage in orange juice. Part 1 participants receive Regimens A, B, C, D and E in a sequential manner.
Part 1: Regimen EEXPERIMENTALAn optional regimen of one low dose tablet of the selected Arbaclofen Placarbil MR Prototype administered with 0.6 g/kg of beverage in orange juice. Part 1 participants receive Regimens A, B, C, D and E in a sequential manner.
Part 2: Regimen FEXPERIMENTALOne low dose Arbaclofen Placarbil MR prototype tablet (selected based on review of the data in Part 1) taken under fasting conditions. Part 2 participants receive Regimens F, G, H, I and J in a sequential manner.
Part 2: Regimen GACTIVE_COMPARATOROne low dose Arbaclofen Placarbil IR capsule taken under fasting conditions as the reference product. Part 2 participants receive Regimens F, G, H, I and J in a sequential manner.
Part 2: Regimen HEXPERIMENTALOne low dose Arbaclofen Placarbil MR prototype tablet (selected based on review of the data in Part 1) taken under fasting conditions. Part 2 participants receive Regimens F, G, H, I and J in a sequential manner.
Part 2: Regimen IEXPERIMENTALOne low dose Arbaclofen Placarbil MR prototype tablet (selected based on review of the data in Part 1) taken under fasting conditions. Part 2 participants receive Regimens F, G, H, I and J in a sequential manner.
Part 2: Regimen JEXPERIMENTALOne low dose Arbaclofen Placarbil MR prototype tablet (selected based on review of the data in Part 1) taken under fasting conditions, or a previously dosed MR prototype in the fed state. Part 2 participants receive Regimens F, G, H, I and J in a sequential manner.
Part 3: Regimen KEXPERIMENTALOne low dose selected Arbaclofen Placarbil MR prototype tablet (selected based on review of the data in Part 2) taken under fasting conditions. Part 3 participants receive Regimens K and L in a randomised crossover manner as the first two treatments, followed by Regimens M and N in a sequential manner.
Part 3: Regimen LEXPERIMENTALOne low dose selected Arbaclofen Placarbil MR prototype tablet administered with 0.6 g/kg of beverage in orange juice or in the fed state, or one mid-low dose of the selected Arbaclofen Placarbil MR prototype tablet. Part 3 participants receive Regimens K and L in a randomised crossover manner as the first two treatments, followed by Regimens M and N in a sequential manner.
Part 3: Regimen MEXPERIMENTALAn optional regimen of one mid-low dose of the selected Arbaclofen Placarbil MR prototype tablet (if not previously dosed in Regimen L) or one mid-high dose of the selected Arbaclofen Placarbil MR prototype tablet taken under fasting conditions. Part 3 participants receive Regimens K and L in a randomised crossover manner as the first two treatments, followed by Regimens M and N in a sequential manner.
Part 3: Regimen NEXPERIMENTALAn optional regimen of one mid-high dose of the selected Arbaclofen Placarbil MR prototype tablet (if not previously dosed in Regimen M) or two mid-low dose of the selected Arbaclofen Placarbil MR prototype tablets. Part 3 participants receive Regimens K and L in a randomised crossover manner as the first two treatments, followed by Regimens M and N in a sequential manner.

Interventions

NameTypeDescription
Arbaclofen PlacarbilDRUGArbaclofen Placarbil
PlaceboDRUGPlacebo matched tablets
Arbaclofen Placarbil SRDRUGOne low dose oral tablet of Arbaclofen Placarbil sustained release (SR) in the fasted state.
Arbaclofen Placarbil MR Prototype ADRUGOne low dose oral tablet pf Arbaclofen Placarbil modified release (MR) Prototype A in the fasted state; this formulation may also be tested with 0.6 g/kg beverage diluted in orange juice
Arbaclofen Placarbil MR Prototype BDRUGOne low dose oral tablet of Arbaclofen Placarbil modified release (MR) Prototype B; this formulation may also be tested with 0.6 g/kg beverage diluted in orange juice
Arbaclofen Placarbil IRDRUGOne low dose oral capsule of Arbaclofen Placarbil immediate release (IR) in the fasted state.
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Eligibility Criteria

Age Range18 Years to 65 Years
SexALL
Healthy VolunteersNo
Study Sites1

Inclusion Criteria: 1. 18 to 65 years of age. 2. Diagnosis of AUD confirmed by the Mini-International Neuropsychiatric Interview. 3. For those requiring medical detoxification from alcohol, subjects will be required to have completed a program for detoxification from alcohol within 4 days prior to ...

Countries:United StatesUnited Kingdom
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Frequently asked questions about Arbaclofen Placarbil

What is Arbaclofen Placarbil used for?

Arbaclofen Placarbil is an investigational small molecule being studied for Alcohol Use Disorder. It is also used in clinical trials involving healthy volunteers to assess the bioavailability of modified release formulations. The drug is in Phase 2 development for the alcohol use disorder indication.

Who makes Arbaclofen Placarbil?

Arbaclofen Placarbil is being developed by Indivior Pharmaceuticals, Inc., which trades under the ticker INDV. The company is conducting clinical trials to evaluate the drug's safety and tolerability in subjects with Alcohol Use Disorder.

What phase is Arbaclofen Placarbil in?

Arbaclofen Placarbil is in Phase 2 clinical development for Alcohol Use Disorder. It has completed a Phase 2 dose-escalation study and a Phase 1 bioavailability study. The drug remains investigational and has not been approved by regulatory authorities.

What clinical trials is Arbaclofen Placarbil in?

Arbaclofen Placarbil has been studied in two completed trials. NCT02511886 was a Phase 2 dose-escalation study in 18 subjects with Alcohol Use Disorder in the United States. NCT03058237 was a Phase 1 bioavailability study in 40 healthy volunteers in the United Kingdom.

Is Arbaclofen Placarbil FDA approved?

Arbaclofen Placarbil is not FDA approved. It is an investigational drug currently in clinical development for Alcohol Use Disorder. The completed trials include a Phase 2 study and a Phase 1 study, but the drug has not yet received marketing approval.