Phase 1
Completed N=50
A Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Escalating Multiple Doses of TAK-831 in Healthy Participants
Healthy
Source: ClinicalTrials.gov NCT03224325 ↗
Enrolled (actual)
50
Serious AEs
0.0%
Results posted
Nov 2019
Primary outcomePrimary: Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event (TEAE) — 69.2; 83.3; 100.0; 66.7 percentage of participants
Summary
The purpose of this study is to evaluate the safety and tolerability of TAK-831 when administered as multiple oral doses at escalating dose levels in healthy participants.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event (TEAE) |
69.2; 83.3; 100.0; 66.7; 100.0; 100.0 | — |
| PRIMARY Percentage of Participants Who Met the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Postdose |
0; 0; 16.7; 0; 16.7; 0 | — |
| PRIMARY Percentage of Participants Who Met the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose |
92.3; 83.3; 100; 66.7; 83.3; 66.7 | — |
| PRIMARY Percentage of Participants Who Met the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Postdose |
38.5; 83.3; 66.7; 16.7; 66.7; 66.7 | — |
| SECONDARY Cmax: Maximum Observed Plasma Concentration for TAK-831 |
242.2; 566.7; 1008.8; 140.0; 1721.2; 2682.9 | — |
| SECONDARY Cmax ss: Maximum Observed Steady-state Plasma Concentration During a Dosing Interval for TAK-831 |
220.8; 528.2; 1494.0; 165.0; 2048.3; 3351.7 | — |
| SECONDARY Tmax: Time of First Occurrence of Cmax for TAK-831 |
0.760; 1.265; 1.775; 0.500; 2.000; 2.020 | — |
| SECONDARY AUC0-24: Area Under the Plasma Concentration-time Curve During a Dosing Interval for TAK-831 |
547.7; 1660.6; 3715.0; 212.7; 7732.2; 10053.7 | — |
Eligibility Criteria
Inclusion Criteria
- Has at least 45 kg weight and has a body mass index (BMI) from 18.0 to 30.0 kilogram per square meter (kg/m^2), inclusive at Screening.
- The participant is a healthy male or female not of childbearing potential adult who is aged 18 to 55 years, inclusive, at the time of informed consent and first study drug dose.
- A male participant who is non-sterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 90 days plus half-lives (95 days) after last study drug dose.
- A female participant with no childbearing potential, defined as a participant that has been surgically sterilized (hysterectomy, bilateral oophorectomy or tubal ligation) or who is postmenopausal (defined as continuous amenorrhea of at least 12 months and follicle stimulating hormone [FSH] greater than [>] 40 international unit per liter [IU/L]).
Exclusion Criteria
- Has a positive urine drug result for drugs of abuse (defined as any illicit drug use) at Screening or Check-in.
- Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse (defined as >3 drinks per day) within 5 years before the Screening visit or is unwilling to agree to abstain from alcohol and drugs throughout the study. (1 drink=12 ounce [oz]. beer=5 oz. wine=1.5 oz. liquor.)
- Has a QT interval with Fridericia's correction method (QTcF) >450 milliseconds (ms) (male participants) or >470 ms (female participants) or PR outside the range of 120 to 220 ms, confirmed with 1 repeat testing, at the Screening Visit or Check-in. When triplicate electrocardiogram (ECG) assessments are collected, the mean of the 3 QTcF and PR values should be used to assess this criterion.
- Has a positive test result for hepatitis B surface antigen (HBsAg), anti- human chorionic gonadotropin (HCV), or human immunodeficiency virus (HIV) antibody/antigen at Screening.
- Has used nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patch or nicotine gum) within 28 days before Check-in. Cotinine test is positive at Screening or Check-in.
- Has poor peripheral venous access.
- Has donated or lost 450 milliliter (mL) or more of his or her blood volume (including plasmapheresis), or had a transfusion of any blood product within 45 days before the first dose of study medication.
- Has a Screening or Check-in abnormal (clinically significant) ECG. Entry of any participant with an abnormal (not clinically significant) ECG must be approved and documented by signature by the principal investigator or designee.
- Has a supine blood pressure outside 90 to 140 millimeter of mercury (mm Hg) for systolic and 50 to 90 mm Hg for diastolic, confirmed on repeat testing within a maximum of 30 minutes, at the Screening Visit or Check-in.
- Has a resting heart rate outside 40 to 100 beats per minute confirmed on repeat testing within a maximum of 30 minutes, at the Screening Visit or Check-in (heart rate from the ECG does not apply).
- Has a risk of suicide according to the Investigator's clinical judgment (example, per Columbia-Suicide Severity Rating Scale [C-SSRS]), or has scored "yes" on item 4 or item 5 of the Suicidal Ideation section of the C-SSRS, if this ideation occurred in the past 6 months, or "yes" on any item of the Suicidal Behavior section, except for the "Non-Suicidal Self-Injurious Behavior", if this behavior occurred in the past 2 years.
Additional Exclusion Criteria for Cohort(s) with cerebrospinal fluid (CSF) Collection:
- Has had CSF collection performed within 30 days before Check-in.
- Has a history of clinically significant back pain and/or injury.
- Has local infection at the puncture site.
- Has thrombocytopenia or other suspected bleeding tendencies noted before procedure.
- Has developed signs and symptoms of spinal radiculopathy, including l
Data sourced from ClinicalTrials.gov (NCT03224325). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.