TAK-935 Multiple Rising Dose Study in Healthy Participants

Epilepsy Clinical Trial

Official title:

A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Safety, Tolerability and Pharmacokinetic Study of Escalating Multiple Doses of TAK-935 in Healthy Subjects

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02539134
• Other study ID #: TAK-935-1002
• Secondary ID: U1111-1168-6634
• Status: Recruiting
• Phase: Phase 1
• First received: August 31, 2015
• Last updated: December 1, 2015
• Start date: September 2015
• Est. completion date: February 2016

Study information

• Verified date: December 2015
• Source: Takeda
• Contact: Takeda Study Registration Call Center
• Phone: +1-877-825-3327
• Email: medicalinformation[@]tpna.com
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the safety, tolerability and pharmacokinetics (PK) of multiple rising doses of TAK-935 in healthy participants.

Description:

The drug being tested in this study is called TAK-935. This study will look at the pharmacokinetics, safety and tolerability of TAK-935 in healthy participants. The study will enroll approximately 56 participants. Participants will be randomly assigned (by chance, like flipping a coin) to 1 of the 5 cohorts in Part 1, which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need): • Part 1, Cohort 1: TAK-935 100 mg once daily (QD) • Part 1, Cohort 2: TAK-935 300 mg QD• Part 1, Cohort 3: TAK-935 300 mg twice daily (BID) • Part 1, Cohort 4: TAK-935 600 mg QD • Part 1, Cohort 5: TAK-935 900 to 1350 mg QD.

Participants will be asked to take the oral solution once or twice a day at the same time for 14 days. An optional Part 2 may be conducted for collecting data to assess the engagement by TAK-935 of the central molecular target cholesterol 24S-hydroxylase (CH24H) by measuring the changes of levels of the metabolite 24S-hydroxycholesterol (24HC). In Part 2, participants will be assigned to up to 2 treatment groups at doses based on the data from other ongoing TAK-935 trials, combined with the safety and tolerability data from Cohorts 1-4 of Part 1.

This single center trial will be conducted in the United States. The overall time to participate in this study will be approximately 30 days. Participants will be admitted in the clinic for the first 14 days, and will be contacted by telephone on Day 28 for a follow-up assessment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 56
• Est. completion date: February 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

All Cohorts

1. Is capable of understanding and complying with protocol requirements.

2. Signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures including requesting that a subject fast for any laboratory evaluations.

3. Is a healthy male or female aged 18 to 55 years inclusive, at the time of informed consent and first study medication dose.

4. Weighs at least 45 kilogram (kg) and has a body mass index (BMI) from 18.0 to 30.0 kilogram per square meter (kg/m^2), inclusive at Screening and Day 1.

5. 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 30 days after last dose.

6. Female participant of childbearing potential who is sexually active with a non-sterilized male partner agrees to use routinely adequate contraception from signing of informed consent and throughout the duration of the study, and for 30 days after the last dose.

7. Can complete the CogState Battery at Screening.

Additional Inclusion Criteria for Subjects undergoing cerebrospinal fluid (CSF) Sampling (Part 2 only):

8. Agrees to spinal tap procedures for CSF collection.

Exclusion Criteria:

All Cohorts

1. Has received any investigational compound within 30 days prior to randomization.

2. Has received TAK-935 in a previous clinical study or as a therapeutic agent.

3. Has a significant history of uncontrolled, clinically significant neurologic (including seizure disorders), cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, endocrine disease or psychiatric disorder or endocrine disease or other abnormality or any significant results from physical examinations, or clinical laboratory results which may impact the ability of the subject to participate or potentially confound the study results. It is the responsibility of the investigator to assess the clinical significance; however, consultation with the Takeda Medical Monitor may be warranted.

4. Has a known hypersensitivity to any component of the formulation of TAK-935.

5. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 1year prior to the screening visit or is unwilling to agree to abstain from alcohol and drugs throughout the study. One unit is equivalent to a half-pint of beer or a single measure of spirits or 1 small glass of wine.

6. Has taken any excluded medication, supplements, or food products during the time periods listed in the Excluded Medications and Dietary Products table.

Additional Exclusion Criteria for Subjects undergoing CSF sampling (Part 2)

7. Has CSF collection performed within 30 days prior to check-in (Day -3).

8. Has a known hypersensitivity to the anesthetic or its derivatives used during CSF collection, or any medication used to prepare the area of lumbar puncture.

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

10. Has a history of clinically significant back pain and/or injury.

11. Has local infection at the puncture site.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)

Related Conditions & MeSH terms

• Epilepsy

Intervention

Drug:
• TAK-935
TAK-935 oral solution
• Placebo
TAK-935 placebo-matching oral solution

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants who Experience at Least one Treatment Emergent Adverse Event (TEAE)	An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.	Baseline up to Day 28	Yes
Primary	Percentage of Participants who Meet the Takeda Global Research and Development Center, Inc. (TGRD) Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose	The percentage of participants with any markedly abnormal standard safety laboratory values collected throughout study.	Baseline up to Day 15	Yes
Primary	Percentage of Participants who Meet the TGRD Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose.	The percentage of participants who meet markedly abnormal criteria designated by TGRD. Vital signs will include oral body temperature, supine and standing blood pressure and respiratory rate.	Baseline up to Day 15	Yes
Primary	Percentage of Participants who Meet the TGRD Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose	The percentage of participants who meet markedly abnormal criteria designated by TGRD measured throughout study.	Baseline up to Day 15	Yes
Secondary	Cmax: Maximum Observed Plasma Concentration for TAK-935	Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.	Days 1 and 14: Predose (up to 30 minutes prior to dose), 10, 15, 20 and 30 minutes, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, and 24 hours postdose	No
Secondary	AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-935	AUC(0-tlqc) is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration (AUC[0-tlqc]).	Days 1 and 14: Predose (up to 30 minutes prior to dose), 10, 15, 20 and 30 minutes, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, and 24 hours postdose	No
Secondary	AUC(0-inf): Area Under the Plasma Concentration-Time Curve from Time 0 to Infinity for TAK-935	AUC (0-inf) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity.	Day 1: Predose (up to 30 minutes prior to dose), 10, 15, 20 and 30 minutes, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, and 24 hours postdose	No
Secondary	AUC(0-tau): Area Under the Plasma Concentration-Time Curve from Time 0 to Time tau Over the Dosing Interval for TAK-935	Area under the plasma concentration-time curve during a dosing interval, where tau is the length of the dosing interval (24 hours for once daily dosing and 12 hours for twice daily dosing).	Day 14: Predose (up to 30 minutes prior to dose), 10, 15, 20 and 30 minutes, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, and 24 hours postdose	No