- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04015687
A Study to Evaluate the Effect of AG-881 on the Pharmacokinetics of a Single Dose of Lamotrigine in Healthy Adults
October 11, 2019 updated by: Agios Pharmaceuticals, Inc.
A Phase 1, Open-label Study to Evaluate the Effect of AG-881 on the Pharmacokinetics of a Single Dose of Lamotrigine in Healthy Adult Subjects
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
22
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Arizona
-
Tempe, Arizona, United States, 85283
- Celerion, Inc
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 55 years (Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
Inclusion criteria
- Healthy, adult, male or female participants, 18-55 years of age, inclusive, at screening;
- Continuous non-smoker who has not used nicotine-containing products for at least 3 months prior to the first dosing and throughout the study, based on participant self-reporting;
- Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kilograms per square meter (kg/m^2) at screening;
- Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or electrocardiograms (ECG), as deemed by the principal investigator or designee;
- Liver function tests (serum alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP], and bilirubin [total and direct]) must be ≤ the upper limit of normal;
Female participants must be of non-childbearing potential defined as a female who has undergone one of the following sterilization procedures at least 6 months prior to the first dosing:
- hysteroscopic sterilization;
- bilateral tubal ligation or bilateral salpingectomy;
- hysterectomy;
- bilateral oophorectomy;
- or is postmenopausal with amenorrhea for at least 1 year prior to the first dosing and follicle-stimulating hormone (FSH) serum levels consistent with postmenopausal status;
- A non-vasectomized, male participant must agree to use a condom with spermicide or abstain from sexual intercourse during the study until 90 days after the last dosing. (No restrictions are required for a vasectomized male provided his vasectomy has been performed 4 months or more prior to the first dosing of study drug. A male who has been vasectomized less than 4 months prior to study first dosing must follow the same restrictions as a non-vasectomized male);
- If a male participant, must agree not to donate sperm from the first dosing until 90 days after the last dosing;
- Understands the study procedures in the informed consent form (ICF), and be willing and able to comply with the protocol.
Exclusion criteria:
- Participant is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study;
- History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the principal investigator or designee;
- History of any illness that, in the opinion of the principal investigator or designee, might confound the results of the study or pose an additional risk to the participant (e.g., history or presence of rashes) by their participation in the study;
- History or presence of ventricular dysfunction or risk factors for Torsades de Pointes (e.g., heart failure, hypokalemia, cardiomyopathy, family history of Long QT Syndrome), in the opinion of the principal investigator or designee;
- History or presence of alcoholism or drug abuse within the past 2 years prior to the first dosing;
- History or presence of hypersensitivity or idiosyncratic reaction to the study drugs or related compounds;
- Known medical history of progressive multifocal leukoencephalopathy;
- Presence of an active skin rash;
- Any positive responses on the Columbia-suicide severity rating scale (C-SSRS);
- Female participants of childbearing potential;
- Female participants with a positive pregnancy test or who are lactating;
- Positive urine drug or alcohol results at screening or first check-in;
- Positive results at screening for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies;
- Corrected QT interval by Fridericia (QTcF) is >450 milliseconds (msec), or Q wave, R wave, and S wave complex (QRS) interval >110 msec, or P wave to the start of the QRS complex (PR interval) >220 msec or participants who have ECG findings deemed abnormal with clinical significance by the principal investigator or designee at screening;
- Estimated creatinine clearance <90 millimeters per minute (mL/min) at screening;
Unable to refrain from or anticipate the use of:
- Any drug, including prescription and non-prescription medications, herbal remedies, and vitamin supplements, beginning 14 days prior to the first dosing and throughout the study. After first dosing, ibuprofen (1.2 grams [g] per 24 hours) may be administered at the discretion of principal investigator or designee;
- Any drugs known to be strong inducers of cytochrome P450 (CYP) 3A enzymes or uridine 5´-diphospho-glucuronyl transferases (UGTs), including St. John's Wort, for 28 days prior to the first dosing and throughout the study. Appropriate sources (e.g., Flockhart Table™) will be consulted to confirm lack of pharmacokinetic/pharmacodynamic interaction with study drug;
- Refuses to abstain from grapefruit-containing foods or beverages or Seville orange containing foods or beverages from 14 days prior to the first dosing and throughout the study;
- Has been on a diet incompatible with the on-study diet, in the opinion of the principal investigator or designee, within the 30 days prior to the first dosing and throughout the study;
- Donation of blood or significant blood loss within 56 days prior to the first dose;
- Plasma donation within 7 days prior to the first dose;
- Participation in another clinical study within 30 days prior to the first dose. The 30-day window will be derived from the date of the last blood collection or dosing, whichever is later, in the previous study to Day 1 of the current study.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: AG-881 (Group 1)
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.
|
Supplied as uncoated tablets.
Supplied as tablets of LAMICTAL® or generic equivalent.
Other Names:
|
Experimental: AG-881 (Group 2)
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.
|
Supplied as uncoated tablets.
Supplied as tablets of LAMICTAL® or generic equivalent.
Other Names:
|
Experimental: AG-881 (Group 3)
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.
|
Supplied as uncoated tablets.
Supplied as tablets of LAMICTAL® or generic equivalent.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Area under the Concentration-time Curve from Time 0 to Infinity (AUC0-inf) for Lamotrigine Administered with Interacting Drug AG-881
Time Frame: At multiple time points daily from Day 14 to Day 21 (or early discontinuation) in Period 2 (21-day period)
|
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
Time Frame: At multiple time points daily from Day 1 to Day 8 in Period 1 (8-day period)
|
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
Time Frame: At multiple time points daily from Day 14 to Day 21 (or early discontinuation) in Period 2 (21-day period)
|
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
Time Frame: At multiple time points daily from Day 1 to Day 8 in Period 1 (8-day period)
|
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
Time Frame: At multiple time points daily from Day 14 to Day 21 (or early discontinuation) in Period 2 (21-day period)
|
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
Time Frame: At multiple time points daily from Day 1 to Day 8 in Period 1 (8-day period)
|
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
Time Frame: At multiple time points daily from Day 14 to Day 21 (or early discontinuation) in Period 2 (21-day period)
|
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
Time Frame: At multiple time points daily from Day 1 to Day 8 in Period 1 (8-day period)
|
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
Time Frame: At multiple time points daily from Day 14 to Day 21 (or early discontinuation) in Period 2 (21-day period)
|
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
Time Frame: At multiple time points daily from Day 1 to Day 8 in Period 1 (8-day period)
|
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
Time Frame: At multiple time points daily from Day 14 to Day 21 (or early discontinuation) in Period 2 (21-day period)
|
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
Time Frame: At multiple time points daily from Day 1 to Day 8 in Period 1 (8-day period)
|
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
Time Frame: At multiple time points daily from Day 14 to Day 21 (or early discontinuation) in Period 2 (21-day period)
|
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
Time Frame: At multiple time points daily from Day 1 to Day 8 in Period 1 (8-day period)
|
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
Time Frame: At multiple time points daily from Day 14 to Day 21 (or early discontinuation) in Period 2 (21-day period)
|
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
Time Frame: At multiple time points daily from Day 1 to Day 8 in Period 1 (8-day period)
|
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
Time Frame: At multiple time points daily from Day 14 to Day 21 (or early discontinuation) in Period 2 (21-day period)
|
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
Time Frame: At multiple time points daily from Day 1 to Day 8 in Period 1 (8-day period)
|
At multiple time points daily from Day 1 to Day 8 in Period 1 (8-day period)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants with Adverse Events (AEs)
Time Frame: 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.
|
Up to approximately 4 weeks
|
Columbia-suicide Severity Rating Scale (C-SSRS)
Time Frame: 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).
|
Up to approximately 4 weeks
|
Percentage of Participants with Abnormalities in 12-lead Electrocardiograms (ECGs)
Time Frame: Up to approximately 4 weeks
|
Up to approximately 4 weeks
|
|
Percentage of Participants with Abnormalities in Vital Sign Measurements
Time Frame: Up to approximately 4 weeks
|
Vital signs will include body temperature, respiratory rate, blood pressure, and heart rate.
|
Up to approximately 4 weeks
|
Percentage of Participants with Abnormalities in Clinical Laboratory Tests
Time Frame: Up to approximately 4 weeks
|
Clinical laboratory assessments will include hematology, serum chemistry, coagulation, and urinalysis.
|
Up to approximately 4 weeks
|
Percentage of Participants with Abnormalities in Physical Examinations
Time Frame: Up to approximately 4 weeks
|
Up to approximately 4 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Medical Affairs, Agios Pharmaceuticals, Inc.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
July 15, 2019
Primary Completion (Actual)
October 9, 2019
Study Completion (Actual)
October 9, 2019
Study Registration Dates
First Submitted
July 3, 2019
First Submitted That Met QC Criteria
July 9, 2019
First Posted (Actual)
July 11, 2019
Study Record Updates
Last Update Posted (Actual)
October 14, 2019
Last Update Submitted That Met QC Criteria
October 11, 2019
Last Verified
October 1, 2019
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Antipsychotic Agents
- Tranquilizing Agents
- Psychotropic Drugs
- Membrane Transport Modulators
- Anticonvulsants
- Sodium Channel Blockers
- Calcium-Regulating Hormones and Agents
- Calcium Channel Blockers
- Lamotrigine
Other Study ID Numbers
- AG881-C-006
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Healthy Participants
-
PfizerRecruitingHealthy Subjects | Healthy ParticipantsUnited States
-
Insmed IncorporatedRecruitingHealthy ParticipantsUnited States
-
Aeovian Pharmaceuticals, Inc.RecruitingHealthy ParticipantsAustralia
-
Suzhou Zelgen Biopharmaceuticals Co.,LtdRecruitingHealthy ParticipantsChina
-
CelgeneNot yet recruitingHealthy ParticipantsUnited States
-
Bristol-Myers SquibbRecruiting
-
AstraZenecaParexelRecruiting
-
ProMis Neurosciences, IncRecruiting
-
Novo Nordisk A/SRecruitingHealthy ParticipantsCanada
-
Novo Nordisk A/SRecruiting
Clinical Trials on AG-881
-
Agios Pharmaceuticals, Inc.Completed
-
ServierServier Pharmaceuticals, LLCAvailablePathologic Processes | Glioma | Neoplasms | Neoplasms by Histologic Type | Neoplasms, Glandular and Epithelial | Recurrence | Disease Attributes | Neoplasms, Germ Cell and Embryonal | Neoplasms, Neuroepithelial | Neuroectodermal Tumors | Neoplasms, Nerve Tissue
-
Institut de Recherches Internationales ServierActive, not recruitingRecurrent Glioma | Grade 2 Glioma | Residual GliomaUnited States, Canada, Spain, Italy, United Kingdom, Switzerland, Israel, Japan, Netherlands, Germany, France
-
Institut de Recherches Internationales ServierCompleted
-
Institut de Recherches Internationales ServierMerck Sharp & Dohme LLCRecruiting
-
Vedic Lifesciences Pvt. Ltd.Enovate Biolife Pvt LtdCompleted
-
Swiss Federal Institute of TechnologyCompletedBlood Iron Isotope EnrichmentSwitzerland
-
Boehringer IngelheimCompletedEarly Parkinson Disease (Early PD)United States, Argentina, Austria, Czech Republic, Finland, Germany, Hungary, India, Japan, Malaysia, Russian Federation, Slovakia, Taiwan, Ukraine
-
Boehringer IngelheimCompletedParkinson DiseaseAustria, Czech Republic, Hungary, India, Italy, Korea, Republic of, Philippines, Poland, Russian Federation, Slovakia, Spain, Sweden, Ukraine, United Kingdom
-
Agios Pharmaceuticals, Inc.Completed