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Healthy ParticipantsPhase 1NCT04015687

A Study to Evaluate the Effect of AG-881 on the Pharmacokinetics of a Single Dose of Lamotrigine in Healthy Adults

A Phase 1 study testing AG-881 and Lamotrigine in people with Healthy Participants, run by Agios Pharmaceuticals, Inc. at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for
Healthy Participants
What is being tested?
AG-881 and Lamotrigine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
1 siteUnited States
Study dates
15 Jul 2019to 9 Oct 2019
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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:
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  • 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.

Who cannot join

  • 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;
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  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Celerion, Inc

    Tempe, Arizona, 85283

Other trials in United States

About this study

Official title: 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.

Being tested
AG-881, Lamotrigine
Keywords
Pharmacokinetic study

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AG-881Drug

    Supplied as uncoated tablets.

  • LamotrigineDrug

    Also called LAMICTAL®

    Supplied as tablets of LAMICTAL® or generic equivalent.

Study groups in NCT04015687
Study groupRoleWhat they receive
AG-881 (Group 1)ExperimentalOn 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.
Receives: Drug: AG-881; Drug: Lamotrigine
AG-881 (Group 2)ExperimentalFollowing 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.
Receives: Drug: AG-881; Drug: Lamotrigine
AG-881 (Group 3)ExperimentalFollowing 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.
Receives: Drug: AG-881; Drug: Lamotrigine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Area under the Concentration-time Curve from Time 0 to Infinity (AUC0-inf) for Lamotrigine Administered with Interacting Drug AG-881

    Measured: At multiple time points daily from Day 14 to Day 21 (or early discontinuation) in Period 2 (21-day period)

  2. Area under the Concentration-time Curve from Time 0 to Infinity (AUC0-inf) for Lamotrigine Administered without Interacting Drug AG-881

    Measured: At multiple time points daily from Day 1 to Day 8 in Period 1 (8-day period)

  3. Maximum Observed Plasma Concentration (Cmax) for Lamotrigine Administered with Interacting Drug AG-881

    Measured: At multiple time points daily from Day 14 to Day 21 (or early discontinuation) in Period 2 (21-day period)

  4. Maximum Observed Plasma Concentration (Cmax) for Lamotrigine Administered without Interacting Drug AG-881

    Measured: At multiple time points daily from Day 1 to Day 8 in Period 1 (8-day period)

  5. 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

    Measured: At multiple time points daily from Day 14 to Day 21 (or early discontinuation) in Period 2 (21-day period)

  6. 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

    Measured: At multiple time points daily from Day 1 to Day 8 in Period 1 (8-day period)

  7. Percent of AUC0-inf Extrapolated (AUC%extrap) for Lamotrigine Administered with Interacting Drug AG-881

    Measured: At multiple time points daily from Day 14 to Day 21 (or early discontinuation) in Period 2 (21-day period)

  8. Percent of AUC0-inf Extrapolated (AUC%extrap) for Lamotrigine Administered without Interacting Drug AG-881

    Measured: At multiple time points daily from Day 1 to Day 8 in Period 1 (8-day period)

  9. Time to Maximum Observed Plasma Concentration (Tmax) for Lamotrigine Administered with Interacting Drug AG-881

    Measured: At multiple time points daily from Day 14 to Day 21 (or early discontinuation) in Period 2 (21-day period)

  10. Time to Maximum Observed Plasma Concentration (Tmax) for Lamotrigine Administered without Interacting Drug AG-881

    Measured: At multiple time points daily from Day 1 to Day 8 in Period 1 (8-day period)

  11. Apparent Terminal Elimination Rate Constant (Kel) for Lamotrigine Administered with Interacting Drug AG-881

    Measured: At multiple time points daily from Day 14 to Day 21 (or early discontinuation) in Period 2 (21-day period)

  12. Apparent Terminal Elimination Rate Constant (Kel) for Lamotrigine Administered without Interacting Drug AG-881

    Measured: At multiple time points daily from Day 1 to Day 8 in Period 1 (8-day period)

  13. Apparent Terminal Elimination Half-life (t½) for Lamotrigine Administered with Interacting Drug AG-881

    Measured: At multiple time points daily from Day 14 to Day 21 (or early discontinuation) in Period 2 (21-day period)

  14. Apparent Terminal Elimination Half-life (t½) for Lamotrigine Administered without Interacting Drug AG-881

    Measured: At multiple time points daily from Day 1 to Day 8 in Period 1 (8-day period)

  15. Apparent Total Plasma Clearance after Oral (Extravascular) Administration (CL/F) for Lamotrigine Administered with Interacting Drug AG-881

    Measured: At multiple time points daily from Day 14 to Day 21 (or early discontinuation) in Period 2 (21-day period)

  16. Apparent Total Plasma Clearance after Oral (Extravascular) Administration (CL/F) for Lamotrigine Administered without Interacting Drug AG-881

    Measured: At multiple time points daily from Day 1 to Day 8 in Period 1 (8-day period)

  17. Apparent Volume of Distribution during the Terminal Elimination Phase after Oral (Extravascular) Administration (Vz/F) for Lamotrigine Administered with Interacting Drug AG-881

    Measured: At multiple time points daily from Day 14 to Day 21 (or early discontinuation) in Period 2 (21-day period)

  18. Apparent Volume of Distribution during the Terminal Elimination Phase after Oral (Extravascular) Administration (Vz/F) for Lamotrigine Administered without Interacting Drug AG-881

    Measured: At multiple time points daily from Day 1 to Day 8 in Period 1 (8-day period)

Secondary outcomes (6)
  1. Percentage of Participants with Adverse Events (AEs)

    An AE is any untoward medical occurrence associated with the use of a drug, whether or not considered drug-related.

    Measured: Up to approximately 4 weeks

  2. Columbia-suicide Severity Rating Scale (C-SSRS)

    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).

    Measured: Up to approximately 4 weeks

  3. Percentage of Participants with Abnormalities in 12-lead Electrocardiograms (ECGs)

    Measured: Up to approximately 4 weeks

  4. Percentage of Participants with Abnormalities in Vital Sign Measurements

    Vital signs will include body temperature, respiratory rate, blood pressure, and heart rate.

    Measured: Up to approximately 4 weeks

  5. Percentage of Participants with Abnormalities in Clinical Laboratory Tests

    Clinical laboratory assessments will include hematology, serum chemistry, coagulation, and urinalysis.

    Measured: Up to approximately 4 weeks

  6. Percentage of Participants with Abnormalities in Physical Examinations

    Measured: Up to approximately 4 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Jul 2019
  2. Study start15 Jul 2019
  3. Primary completion9 Oct 2019
  4. Study completion9 Oct 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Basic science
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04015687
Sponsor's protocol ID
AG881-C-006
Status last verified
Oct 2019
First submitted
3 Jul 2019
Last updated
14 Oct 2019
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AG-881 and Lamotrigine in people with Healthy Participants, run by Agios Pharmaceuticals, Inc. at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). The study lists 18 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2019.

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