Bioavailability and Effect of Food on TAK-385 Tablet Formulations in Healthy Participants

Phase 1

Completed

• Conditions: Healthy Volunteers
• Interventions: Drug: TAK-385 T2 Formulation; Drug: TAK-385 T4 Formulation B; Drug: TAK-385 T4 Formulation C

• Registration Number: NCT02396147
• Lead Sponsor: Takeda

Brief Summary

The purpose of this study is to evaluate the oral bioavailability of two new tablet formulations of TAK-385 (T4 Formulation B and T4 Formulation C) under fasted and fed conditions, relative the T2 Formulation tablet; and to estimate the effect of food on the pharmacokinetics (PK) of a single oral dose of the T4 Formulation B tablet and the T4 Formulation C tablet.

Detailed Description

The drug being tested in this study is called TAK-385. In this study, two new formulations of TAK-385 are being evaluated under fasted and fed conditions, relative to a previous formulation of TAK-385, to assess its bioavailability and how it is processed by the body. This study will look at lab results of people who take TAK-385.

The study will enroll approximately 54 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups (Arms). Participants in Arm 1 will receive TAK-385 T2 Formulation 120 mg tablet (80mg + 40mg tablets) under fasted conditions, TAK-385 T4 Formulation B 120 mg tablet under fasted conditions, and TAK-385 T4 Formulation B 120 mg tablet under fed conditions. Participants in Arm 2 will receive TAK-385 T2 Formulation 120 mg tablet (80mg + 40mg tablets) under fasted conditions, TAK-385 T4 Formulation C 120 mg tablet under fasted conditions, and TAK-385 T4 Formulation C 120 mg tablet under fed conditions. Participants in each arm will be randomized to receive study drug in one of 6 treatment sequences. Study medication will be administered as a single dose on Days 1, 11 and 21. There will be a 10-day washout period between each dose.

This single-centre trial will be conducted in the United States. The overall time to participate in this study is 51 days. Participants will make 10 visits to the clinic, including three 4-day periods of confinement to the clinic, and will be contacted by telephone 30 days after last dose of study drug for a follow-up assessment.

Study Timeline

• Study Start: 2015-03
• Study First Submitted: 2015-03-18
• Study First Submitted QC: 2015-03-23
• Study First Posted: 2015-03-24
• Primary Completion: 2015-04
• Study Completion: 2015-06
• Status Verified: 2016-06
• Results First Submitted: 2016-06-09
• Results First Submitted QC: 2016-06-09
• Last Update Submitted: 2016-06-09
• Results First Posted: 2016-07-25
• Last Update Posted: 2016-07-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 54

Inclusion Criteria

1. Age 18 to 55 years, inclusive, at the time of consent.

2. Healthy adult male, as determined by a physician evaluation that includes:

   • Medical history (ie, no clinically significant medical conditions requiring ongoing drug therapy).
   • Physical examination.
   • Vital signs.
   • Electrocardiogram (ECG).
   • Laboratory evaluation (hematology, biochemistry, and urinalysis).
   • No acute illness within 30 days before screening that required prescription or over-the-counter (OTC) medicines.

3. Weight ≥ 55 kg and body mass index (BMI) between 18.0 and 32.0 kg/m^2 inclusive, at Screening.

4. Nonsmoker for at least 2 years and does not use nicotine-containing products (including, but not limited to, cigarettes, pipes, cigars, chewing tobacco, or nicotine patch or gum).

5. Male participants, even if surgically sterilized (ie, status postvasectomy), who:

   • Agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug, or
   • Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods for the female partner] and withdrawal are not acceptable methods of contraception.)

6. Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care.

7. Suitable venous access for the study-required blood sampling.

8. Abstains from behavior that increases susceptibility to contract blood-borne pathogens (eg, obtaining a tattoo or participating in unsafe needle use for any purpose) during the 28 days before study entry.

9. In the opinion of the investigator, the participant or legal guardian is capable of understanding and complying with protocol requirements.

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Exclusion Criteria

1. Has any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
2. Has received any investigational compound within 30 days (or 5 half- lives of the compound, if longer) before check-in (Day -1).
3. Has received TAK-385 in a previous clinical study.
4. Has current or recent (within 6 months) history of gastrointestinal disease that would be expected to influence the absorption of drugs (ie, history of malabsorption, esophageal reflux, peptic ulcer disease, erosive esophagitis, frequent heartburn, or any surgical intervention).
5. Is lactose intolerant.
6. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse (defined as regular or daily consumption of more than 4 alcoholic drinks per day) within 1 year before screening or is unwilling to agree to abstain from alcohol and drugs throughout the study.
7. Has a positive test result for hepatitis B surface antigen (HBsAG) or hepatitis C virus (HCV) antibody at Screening.
8. Has a positive urine drug result for drugs of abuse or alcohol at Screening or check-in (Day -1).
9. Has taken any prescription medicine or herbal preparations (eg, St. John's wort) or received any immunizations within 30 days before check-in (Day -1).
10. Has taken any OTC medications or vitamin supplements within 14 days before check-in (Day -1). Excluded from this list is occasional use of acetaminophen (paracetamol) ≤ 1 g/day or other medication approved by the sponsor on a case-by-case basis.
11. Is unwilling to agree to abstain from caffeine and food products from 72 hours before check-in (Day -1) to completion of the study.
12. Has a clinically significant electrocardiogram (ECG) abnormality at Screening or check-in (Day -1) or a QTc interval (by the Fridericia correction) of 450 msec or greater. The participant has a history of cardiac disease including, but not limited to, congenital long-QT syndrome, torsades de pointes or torsades de pointes risk factors (eg, cardiac insufficiency, hypokalemia, family history of long-QT syndrome, current use of Class IA [eg, quinidine or procainamide] or Class III [eg, amiodarone or sotalol] antiarrhythmic medications or other medications with known effects on QT interval).
13. Has abnormal laboratory values suggesting a clinically significant disease at Screening or check-in (Day -1) or has abnormalities in the following laboratory parameters: alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) value >1.5 times the upper limit of normal.
14. Has engaged in heavy exercise (marathon running, weight lifting, etc) within 72 hours before check-in (Day -1) or is unwilling to agree to abstain from heavy exercise throughout the study.
15. Has known allergy to TAK-385 or its excipients.
16. Participants who, for any reason, are deemed by the investigator to be inappropriate for this study, including participants who are unable to communicate or to cooperate with the investigator.
17. Any participant who is an immediate family member, investigational site employee, or in a dependent relationship with an investigational site employee who is involved in conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Arm 1: T2-A + T4B-B + T4B-C	TAK-385 T4 Formulation B	T2 Formulation Regimen A (T2-A) TAK-385, 120 mg tablet (80 mg + 40 mg tablets), orally, under fasted conditions, T4 Formulation B Regimen B (T4B-B) TAK-385, 120 mg tablet, orally, under fasted conditions, and T4 Formulation B Regimen C (T4B-C) TAK-385, 120 mg tablet, orally, under fed conditions. There were 6 randomized sequences. Study medication was administered as a single dose on Days 1, 11 and 21. There was a 10-day washout period between each dose.
Arm 1: T2-A + T4B-B + T4B-C	TAK-385 T2 Formulation	T2 Formulation Regimen A (T2-A) TAK-385, 120 mg tablet (80 mg + 40 mg tablets), orally, under fasted conditions, T4 Formulation B Regimen B (T4B-B) TAK-385, 120 mg tablet, orally, under fasted conditions, and T4 Formulation B Regimen C (T4B-C) TAK-385, 120 mg tablet, orally, under fed conditions. There were 6 randomized sequences. Study medication was administered as a single dose on Days 1, 11 and 21. There was a 10-day washout period between each dose.
Arm 2: T2-A + T4C-D + T4C-E	TAK-385 T2 Formulation	T2 Formulation Regimen A (T2-A) TAK-385, 120 mg tablet (80 mg + 40 mg tablets), orally, under fasted conditions, T4 Formulation C Regimen D (T4C-D) TAK-385, 120 mg tablet, orally, under fasted conditions, and T4 Formulation C Regimen E (T4C-E) TAK-385, 120 mg tablet, orally, under fed conditions. There were 6 randomized sequences. Study medication was administered as a single dose on Days 1, 11 and 21. There was 10-day washout period between each dose.
Arm 2: T2-A + T4C-D + T4C-E	TAK-385 T4 Formulation C	T2 Formulation Regimen A (T2-A) TAK-385, 120 mg tablet (80 mg + 40 mg tablets), orally, under fasted conditions, T4 Formulation C Regimen D (T4C-D) TAK-385, 120 mg tablet, orally, under fasted conditions, and T4 Formulation C Regimen E (T4C-E) TAK-385, 120 mg tablet, orally, under fed conditions. There were 6 randomized sequences. Study medication was administered as a single dose on Days 1, 11 and 21. There was 10-day washout period between each dose.

Primary Outcome Measures

Name	Time	Method
AUC(0-120): Area Under the Plasma Concentration-Time Curve From Time 0 to 120 Hours Postdose for TAK-385	Days 1, 11, and 21 predose and at multiple time points (up to 120 hours) post-dose
Cmax: Maximum Observed Plasma Concentration for TAK-385	Days 1, 11, and 21 predose and at multiple time points (up to 120 hours) post-dose
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-385	Days 1, 11, and 21 predose and at multiple time points (up to 120 hours) post-dose

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Shifts From Normal at Baseline in Safety Laboratory Values in More Than 1 Participant	Baseline and Days 4, 10, 14, 20, 24 and 26	Participants with shifts from normal at Baseline in safety laboratory values (Clinical Chemistry, Hematology and Urinalysis) collected throughout study. Low=below normal reference range, Normal=within reference range, High=above normal reference range and Abnormal=outside of normal reference range.
Percentage of Participants With Electrocardiogram (ECG) Parameters Abnormal and Clinically Significant	Days 1, 11, 21 and 26	A 12-lead ECG was administered. The investigator interpreted the ECG using one of the following categories: within normal limits, abnormal but not clinically significant, or abnormal and clinically significant.
Oral Clearance (CL/F) for TAK-385	Days 1, 11, and 21 predose and at multiple time points (up to 120 hours) post-dose
Percentage of Participants With Markedly Abnormal Vital Sign Measurements	From Day 1 to Day 26	The percentage of participants with any markedly abnormal standard vital sign measurements was collected throughout study.
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-385	Days 1, 11, and 21 predose and at multiple time points (up to 120 hours) post-dose
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	From Day 1 to 30 days after the last dose of study drug (Up to 51 days total)	An AE is considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. A SAE is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.
Terminal Phase Elimination Half-Life (T1/2) for TAK-385	Days 1, 11, and 21 predose and at multiple time points (up to 120 hours) post-dose