A Study to Evaluate the Effect of AG-881 on the Pharmacokinetics of a Single Dose of Lamotrigine in Healthy Adults
- Registration Number
- NCT04015687
- Lead Sponsor
- Agios Pharmaceuticals, Inc.
- Brief Summary
The main purpose of this study is to examine the effect of multiple doses of AG-881 on the pharmacokinetics (PK) of a single dose of lamotrigine in healthy adults.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 22
Inclusion Criteria
Not provided
Exclusion Criteria
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description AG-881 (Group 1) AG-881 On Day 1 of Period 1, Group 1 participants will receive a single 50-milligram (mg) oral dose of lamotrigine at Hour 0. In Period 2, they will receive 50-mg oral doses of AG-881 once daily (QD) for 15 consecutive days (Days 1 to 15), with a single 50-mg oral dose of lamotrigine coadministered at Hour 0 on Day 14. AG-881 (Group 1) Lamotrigine On Day 1 of Period 1, Group 1 participants will receive a single 50-milligram (mg) oral dose of lamotrigine at Hour 0. In Period 2, they will receive 50-mg oral doses of AG-881 once daily (QD) for 15 consecutive days (Days 1 to 15), with a single 50-mg oral dose of lamotrigine coadministered at Hour 0 on Day 14. AG-881 (Group 2) AG-881 Following a safety and tolerability review of the data from at least 7 days of AG-881 dosing of Group 1 participants in Period 2, Group 2 participants will receive a single 50-mg oral dose of lamotrigine at Hour 0 in Period 1, and 50-mg oral doses of AG-881 QD for 15 consecutive days (Days 1 to 15), with a single 50-mg oral dose of lamotrigine coadministered at Hour 0 on Day 14 in Period 2. AG-881 (Group 2) Lamotrigine Following a safety and tolerability review of the data from at least 7 days of AG-881 dosing of Group 1 participants in Period 2, Group 2 participants will receive a single 50-mg oral dose of lamotrigine at Hour 0 in Period 1, and 50-mg oral doses of AG-881 QD for 15 consecutive days (Days 1 to 15), with a single 50-mg oral dose of lamotrigine coadministered at Hour 0 on Day 14 in Period 2. AG-881 (Group 3) AG-881 Following a safety and tolerability review of the data from Group 1 participants, and from at least 7 days of AG-881 dosing of Group 2 participants in Period 2, Group 3 participants will receive a single 50-mg oral dose of lamotrigine at Hour 0 in Period 1; and 50-mg oral doses of AG-881 QD for 15 consecutive days (Days 1 to 15) with a single 50-mg oral dose of lamotrigine coadministered at Hour 0 on Day 14 in Period 2. AG-881 (Group 3) Lamotrigine Following a safety and tolerability review of the data from Group 1 participants, and from at least 7 days of AG-881 dosing of Group 2 participants in Period 2, Group 3 participants will receive a single 50-mg oral dose of lamotrigine at Hour 0 in Period 1; and 50-mg oral doses of AG-881 QD for 15 consecutive days (Days 1 to 15) with a single 50-mg oral dose of lamotrigine coadministered at Hour 0 on Day 14 in Period 2.
- Primary Outcome Measures
Name Time Method Area under the Concentration-time Curve from Time 0 to Infinity (AUC0-inf) for Lamotrigine Administered with Interacting Drug AG-881 At multiple time points daily from Day 14 to Day 21 (or early discontinuation) in Period 2 (21-day period) Area under the Concentration-time Curve from Time 0 to Infinity (AUC0-inf) for Lamotrigine Administered without Interacting Drug AG-881 At multiple time points daily from Day 1 to Day 8 in Period 1 (8-day period) Maximum Observed Plasma Concentration (Cmax) for Lamotrigine Administered with Interacting Drug AG-881 At multiple time points daily from Day 14 to Day 21 (or early discontinuation) in Period 2 (21-day period) Maximum Observed Plasma Concentration (Cmax) for Lamotrigine Administered without Interacting Drug AG-881 At multiple time points daily from Day 1 to Day 8 in Period 1 (8-day period) Area under the Concentration-time Curve, from Time 0 to the Last Observed Non-zero Concentration (t) (AUC0-t) for Lamotrigine Administered with Interacting Drug AG-881 At multiple time points daily from Day 14 to Day 21 (or early discontinuation) in Period 2 (21-day period) Area under the Concentration-time Curve, from Time 0 to the Last Observed Non-zero Concentration (t) (AUC0-t) for Lamotrigine Administered without Interacting Drug AG-881 At multiple time points daily from Day 1 to Day 8 in Period 1 (8-day period) Percent of AUC0-inf Extrapolated (AUC%extrap) for Lamotrigine Administered with Interacting Drug AG-881 At multiple time points daily from Day 14 to Day 21 (or early discontinuation) in Period 2 (21-day period) Percent of AUC0-inf Extrapolated (AUC%extrap) for Lamotrigine Administered without Interacting Drug AG-881 At multiple time points daily from Day 1 to Day 8 in Period 1 (8-day period) Time to Maximum Observed Plasma Concentration (Tmax) for Lamotrigine Administered with Interacting Drug AG-881 At multiple time points daily from Day 14 to Day 21 (or early discontinuation) in Period 2 (21-day period) Time to Maximum Observed Plasma Concentration (Tmax) for Lamotrigine Administered without Interacting Drug AG-881 At multiple time points daily from Day 1 to Day 8 in Period 1 (8-day period) Apparent Terminal Elimination Rate Constant (Kel) for Lamotrigine Administered with Interacting Drug AG-881 At multiple time points daily from Day 14 to Day 21 (or early discontinuation) in Period 2 (21-day period) Apparent Terminal Elimination Rate Constant (Kel) for Lamotrigine Administered without Interacting Drug AG-881 At multiple time points daily from Day 1 to Day 8 in Period 1 (8-day period) Apparent Terminal Elimination Half-life (t½) for Lamotrigine Administered with Interacting Drug AG-881 At multiple time points daily from Day 14 to Day 21 (or early discontinuation) in Period 2 (21-day period) Apparent Terminal Elimination Half-life (t½) for Lamotrigine Administered without Interacting Drug AG-881 At multiple time points daily from Day 1 to Day 8 in Period 1 (8-day period) Apparent Total Plasma Clearance after Oral (Extravascular) Administration (CL/F) for Lamotrigine Administered with Interacting Drug AG-881 At multiple time points daily from Day 14 to Day 21 (or early discontinuation) in Period 2 (21-day period) Apparent Total Plasma Clearance after Oral (Extravascular) Administration (CL/F) for Lamotrigine Administered without Interacting Drug AG-881 At multiple time points daily from Day 1 to Day 8 in Period 1 (8-day period) Apparent Volume of Distribution during the Terminal Elimination Phase after Oral (Extravascular) Administration (Vz/F) for Lamotrigine Administered with Interacting Drug AG-881 At multiple time points daily from Day 14 to Day 21 (or early discontinuation) in Period 2 (21-day period) Apparent Volume of Distribution during the Terminal Elimination Phase after Oral (Extravascular) Administration (Vz/F) for Lamotrigine Administered without Interacting Drug AG-881 At multiple time points daily from Day 1 to Day 8 in Period 1 (8-day period)
- Secondary Outcome Measures
Name Time Method Percentage of Participants with Abnormalities in Physical Examinations Up to approximately 4 weeks Percentage of Participants with Adverse Events (AEs) Up to approximately 4 weeks An AE is any untoward medical occurrence associated with the use of a drug, whether or not considered drug-related.
Columbia-suicide Severity Rating Scale (C-SSRS) Up to approximately 4 weeks The C-SSRS is a questionnaire scale to detect emergent suicide symptoms (suicidal ideation or actual suicidal behavior). Questions are either answered yes/no or are on a scale of 1 (low severity) to 5 (high severity).
Percentage of Participants with Abnormalities in 12-lead Electrocardiograms (ECGs) Up to approximately 4 weeks Percentage of Participants with Abnormalities in Vital Sign Measurements Up to approximately 4 weeks Vital signs will include body temperature, respiratory rate, blood pressure, and heart rate.
Percentage of Participants with Abnormalities in Clinical Laboratory Tests Up to approximately 4 weeks Clinical laboratory assessments will include hematology, serum chemistry, coagulation, and urinalysis.
Trial Locations
- Locations (1)
Celerion, Inc
🇺🇸Tempe, Arizona, United States