A Study to Assess the Relative Bioavailability and to Assess the Effect of Food on the Bioavailability of a TAK-648 Tablet in Healthy Participants

A Phase 1, Randomized, Open-Label, Single-Dose, 3-Way Crossover Study to Assess the Relative Bioavailability of a TAK-648 Tablet Compared With a TAK-648 Oral Solution, and to Assess the Effect of Food on the Bioavailability of a TAK-648 Tablet in Healthy Participants

The purpose of this study is to assess the relative bioavailability of a TAK-648 tablet compared with a TAK-648 oral solution, and to assess the effect of food on the bioavailability of a TAK-648 tablet in healthy participants.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: TAK-648 Tablet; Drug: TAK-648 Oral Solution

Detailed Description

This study will assess the relative Bioavailability (BA) of TAK-648 tablet compared with that of TAK-648 solution and the effect of food on the BA of the TAK-648 tablet.

The study will enroll approximately 24 healthy participants. Participants will be randomly assigned to one of the three treatment sequences:

• TAK-648 tablet in fed state, followed by TAK-648 tablet in fasted state, followed by TAK-648 oral solution in fasted state
• TAK-648 tablet in fasted state, followed by TAK-648 oral solution in fasted state, followed by TAK-648 tablet in fed state
• TAK-648 oral solution in fasted state, TAK-648 tablet in fed state, TAK-648 tablet in fasted state The dosing in a period and the subsequent period will be separated by a minimum 7-day washout interval. Participants will be asked to take single dose of TAK-648 tablet or oral solution on Day 1 of each period.

This single-center trial will be conducted in the United States. Participants will make 4 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 Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy male or female aged 18 to 55 years, inclusive, at the time of informed consent and first study medication dose.
2. Weighs at least 50 kilogram (kg) (110 pounds [lbs]) and has a body mass index (BMI) from 18.0 to 30.0 kilogram per square meter (kg/m^2), inclusive at Screening.
3. Has systolic blood pressure greater than (>) 90 and less than or equal to (<=) 150 millimeter of mercury (mmHg) and diastolic blood pressure >60 and <=90 mm Hg at Screening and at Check-in (Day -1) of Period 1. If out of range, may be repeated once for eligibility determination within a maximum of 5 minutes.
4. Has a calculated creatinine clearance >60 milliliter per minute (mL/min) at Screening and Check-in (Day -1) of Period 1.
5. Male participant who is nonsterilized 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 12 weeks after last dose.
6. Female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent and throughout the duration of the study and for 12 weeks after the last dose.

Exclusion Criteria:

1. Has received any investigational compound within 30 days prior to the first dose of study medication.
2. Has received TAK-648 in a previous clinical study or as a therapeutic agent.
3. Is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in the conduct of this study (example, spouse, parent, child, sibling) or may consent under duress.
4. Has any significant medical histories or currently uncontrolled clinical conditions, which may render it unsafe for participant to participate in the study, may impact the ability of the participant to participate in the study, or may potentially confound the study results.
5. Has a history of significant gastrointestinal (GI) disorders manifested with persistent, chronic, or intermittent nausea, vomiting, or diarrhea, or has a current or recent (within 6 months) GI disease that would influence the absorption of drugs.
6. Has diagnosis of major depression, bipolar disorder, or anxiety disorders, or has received any medication to treat any psychological disorders within 1 year.
7. Has a 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 past 6 months prior to screening.
8. Has known hypersensitivity to any component of the formulation of TAK-648, or to a phosphodiesterase type 4 (PDE4) inhibitor (example, roflumilast).
9. Has taken any excluded medication, supplements, or food products during the time periods listed in the Prohibited Medications table.
10. Has abnormal Screening or Check-in (Day -1) of Period 1 laboratory values that suggest a clinically significant underlying disease or participant has the following laboratory abnormalities: Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >2.5* upper limit of normal (ULN).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TAK-648 Sequence ABC; Regimen A TAK-648 0.3 mg, tablet, orally, 30 minutes after a high fat meal, once on Day 1 of Period 1, followed by at least 7 day washout period, followed by Regimen B TAK-648 0.3 mg, tablet, orally, in fasted state, once on Day 1 of Period 2, followed by at least 7 day washout period, followed by Regimen C TAK-648 0.3 mg, solution, orally, in fasted state, once on Day 1 of Period 3.	Drug: TAK-648 Tablet; Tak-648 tablet; Drug: TAK-648 Oral Solution; TAK-648 oral solution
Experimental: TAK-648 Sequence BCA; Regimen B TAK-648 0.3 mg, tablet, orally, in fasted state, once on Day 1 of Period 1, followed by at least 7 day washout period, followed by Regimen C TAK-648 0.3 mg, solution, orally, in fasted state, once on Day 1 of Period 2, followed by at least 7 day washout period, followed by Regimen A TAK-648 0.3 mg, tablet, orally, 30 minutes after a high fat meal, once on Day 1 of Period 3.	Drug: TAK-648 Tablet; Tak-648 tablet; Drug: TAK-648 Oral Solution; TAK-648 oral solution
Experimental: TAK-648 Sequence CAB; Regimen C TAK-648 0.3 mg, solution, orally, in fasted state, once on Day 1 of Period 1, followed by at least 7 day washout period, followed by Regimen A TAK-648 0.3 mg, tablet, orally, after a high fat meal, once on Day 1 of Period 2, followed by at least 7 day washout period, followed by Regimen B TAK-648 0.3 mg, tablet, orally, in fasted state, once on Day 1 of Period 3.	Drug: TAK-648 Tablet; Tak-648 tablet; Drug: TAK-648 Oral Solution; TAK-648 oral solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cmax: Maximum Observed Plasma Concentration for TAK-648	Day 1 pre-dose and multiple timepoints post-dose (Up to 72 hours) in each Period
AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-648	Day 1 pre-dose and multiple timepoints post-dose (Up to 72 hours) in each Period
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-648	Day 1 pre-dose and multiple timepoints post-dose (Up to 72 hours) in each Period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.	First dose of study drug to 30 days after the last dose of study drug (Up to Day 47)
Percentage of Participants With Markedly Abnormal Laboratory Values at Least Once Post-dose		First dose of study drug to 7 days after the last dose of study drug (Up to Day 24)
Percentage of Participants With Markedly Abnormal Vital Sign Values at Least Once Post-dose	Vital signs included body temperature (oral), sitting blood pressure (after 5 minutes resting), respiration rate and pulse (beats per minute [bpm]).	First dose of study drug to 7 days after the last dose of study drug (Up to Day 24)

Collaborators and Investigators

• Sponsor: Takeda

Study record dates

Study Major Dates

• Study Start: June 1, 2015
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: June 19, 2015
• First Submitted That Met QC Criteria: June 19, 2015
• First Posted (Estimate): June 24, 2015

Study Record Updates

• Last Update Posted (Estimate): August 31, 2016
• Last Update Submitted That Met QC Criteria: July 19, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: Drug Therapy
• Other Study ID Numbers: TAK-648-1003; U1111-1170-0503 (Registry Identifier: WHO)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No