A Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), and Pharmacodynamics (PD) of Single and Multiple Oral Dose of TAK-418 in Healthy Female Participants

Healthy Volunteers Clinical Trial

Official title:

A Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Oral Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of TAK-418 in Healthy Female Subjects

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03501069
• Other study ID #: TAK-418-1003
• Secondary ID: U1111-1209-4647
• Status: Terminated
• Phase: Phase 1
• Start date: May 30, 2018
• Est. completion date: December 26, 2018

Study information

• Verified date: June 2020
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to characterize safety and tolerability of TAK-418 in non-Japanese and Japanese healthy female participants when administered at single or multiple (once daily [QD]) oral doses.

Description:

The drug being tested in this study is called TAK-418. This study will assess the safety, tolerability, PK and PD of single and multiple rising doses of TAK-418 in healthy Japanese or non-Japanese females.

The study will enroll approximately 48 participants in 6 cohorts and each cohort will have 8 participants. The study will include 2 parts: single rising dose (SRD) in Cohort 1 and multiple rising dose (MRD) in Cohorts 2 to 6. Cohort 3 will include cerebrospinal fluid (CSF) collection. Participants will be randomly assigned (by chance, like flipping a coin) to one of the 6 cohorts.

This two-center trial will be conducted in the United States. The overall time to participate in Cohort 1 of this study is approximately 105 days and 98 days in Cohort 2. Participants will be contacted by telephone 14 days after last dose of study drug for a follow-up assessment.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 32
• Est. completion date: December 26, 2018
• Est. primary completion date: December 26, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

1. Has a body mass index (BMI) greater than or equal to (>=) 18.5 and less than or equal to (<=) 30.0 kilogram per square meter (kg/m^2) at the Screening Visit. (Cohorts 1 to 4 only).

2. Is a nonsmoker who has not used tobacco- or nicotine-containing products (example, nicotine patch) for at least 6 months before administration of the first dose of trial drug or invasive procedure.

3. The participant either is of nonchildbearing potential, OR, if of childbearing potential, is using a highly effective method of contraception with low user dependency during the entire duration of the study.

For Cohorts 5 and 6 (Japanese participants) only:

1. Has a BMI >=18.0 and <= 26.0 kg/m^2, at the Screening Visit.

Exclusion Criteria:

1. Has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV), or human immunodeficiency virus (HIV) antibody/antigen, at Screening.

2. Had major surgery, donated or lost 1 unit of blood (approximately 500 milliliter [mL]) within 4 weeks before the Screening Visit.

3. Has a history of alcohol consumption exceeding 2 standard drinks per day on average (1 glass is approximately equivalent to beer [354 mL/12 ounces], wine [118 mL/4 ounces], or distilled spirits [29.5 mL/1 ounce] per day).

4. Consumes excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy drinks, or other caffeinated beverages per day.

5. Has a substance abuse disorder.

6. Has risk of suicide according to the investigator's clinical judgment per Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening or has made a suicide attempt in the 6 months before Screening.

7. Has luteinizing hormone (LH), follicle-stimulating hormone (FSH), or estradiol levels that are clinically abnormal.

8. Has a resting heart rate outside of the range of 50 to 100 beats per minute, confirmed on repeat testing within a maximum of 30 minutes, at the Screening Visit or Check-in (Day -1).

For Cohort 3 only (includes CSF sample collection):

1. Has had CSF collection performed within 30 days before Check-in (Day -1).

2. Has significant vertebral deformities (scoliosis or kyphosis) that, in the opinion of the investigator, may interfere with the lumbar puncture procedure.

3. Has a local infection at the puncture site.

4. Has thrombocytopenia or other suspected bleeding tendencies noted before the procedure.

5. Has developed signs and symptoms of spinal radiculopathy, including lower extremity pain and paresthesia.

6. Has any focal neurological deficit that might suggest an increase in intracranial pressure.

7. Has any abnormal finding on ophthalmological assessment/fundoscopy indicative of raised intracranial pressure (that is, optic disc swelling/edema; or [uncontrolled] hypertensive retinopathy).

8. Regularly has moderate-to-severe headaches requiring analgesics.

9. Has any bleeding abnormality or history of bleeding abnormalities.

10. Has abnormal coagulation tests (prothrombin time [PT]/international normalized ratio [INR], partial thromboplastin time [PTT]) at Screening.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• TAK-418
TAK-418 capsules.
• TAK-418 Matching Placebo
TAK-418 matching placebo capsules.

Locations

Country	Name	City	State
United States	Parexel International	Glendale	California
United States	PRA Health Sciences	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Millennium Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cohort 1: Number of Participants Who Experienced at Least One Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Event (SAE)		Baseline up to Day 60
Primary	Cohorts 2 to 5: Number of Participants Who Experienced at Least One TEAEs and SAE		Baseline up to Day 70
Primary	Cohort 1: Number of Participants With Markedly Abnormal Criteria for Clinical Laboratory Values at Least Once Postdose		Baseline up to Day 60
Primary	Cohorts 2 to 5: Number of Participants With Markedly Abnormal Criteria for Clinical Laboratory Values at Least Once Postdose		Baseline up to Day 70
Primary	Cohort 1: Number of Participants With Markedly Abnormal Criteria for Vital Signs at Least Once Postdose		Baseline up to Day 60
Primary	Cohorts 2 to 5: Number of Participants With Markedly Abnormal Criteria for Vital Signs at Least Once Postdose		Baseline up to Day 70
Primary	Cohort 1: Number of Participants Who Meet the Markedly Abnormal Values of 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose		Baseline up to Day 60
Primary	Cohorts 2 to 5: Number of Participants Who Meet the Markedly Abnormal Values of 12-lead ECG Parameters at Least Once Post Dose		Baseline up to Day 70
Secondary	Cohort 1; AUC8: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-418 on Day 1		Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
Secondary	Cohort 2 to 5: AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Over the Dosing Interval for TAK-418 on Days 1 and 10		Days 1 and 10 pre-dose and at multiple time points (up to 24 hours) post-dose
Secondary	Cmax: Maximum Observed Plasma Concentration for TAK-418		Cohort 1: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose; Cohorts 2 to 5: Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose
Secondary	Tmax: Time to Reach the Cmax for TAK-418		Cohort 1: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose; Cohorts 2 to 5: Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose