Clinical trial NCT02723201: TAK-020 Relative Bioavailability and Food Effect Study in Healthy Participants
Official title: A Randomized, Open Label Phase 1 Study in Healthy Volunteers to Evaluate the Relative Bioavailability of a Single Dose of Various Test Solid Formulations of TAK-020 Compared With a Single Dose of Reference Oral Solution and to Evaluate the Food Effect and Potentially the Dose Proportionality of the Optimal Solid Dose Formulation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2016-03-30
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The purpose of this study is to assess the relative bioavailability of solid oral formulations of TAK-020 in comparison with single dose of TAK-020 oral solution formulation and to evaluate the food effect and potentially the dose proportionality of the optimal oral solid formulation.

Detailed description: TAK-020 is being developed for the potential treatment of autoimmune diseases including rheumatoid arthritis. Currently TAK-020 is available as an oral solution. This study is to develop an oral tablet formulation. There are three parts to this study. Part 1 will compare different tablet formulations of TAK-020 compared to a reference oral solution to identify the best tablet formulation to use in Parts 2 and 3. Part 2 will look at the effect food has on TAK-020. Part 3 is optional; its implementation will be decided upon using data from Part 2. It will evaluate whether increased doses of TAK-020 produce an expected proportional increase in the plasma concentration of TAK-020.

In Part 1 participants will receive a single dose of the following:

Period 1: TAK-020 Oral Solution Period 2: TAK-020 Co-Crystal Tablet Period 3: TAK-020 Solid Dispersion Tablet Period 4: TAK-020 Immediate Release Tablet

In Part 2 participants will be split into two groups; one will receive the chosen formulation of TAK-020 in the fasted state followed by the fed state and the other group will receive it in the fed state followed by the fasted state. The dose used in Part 2 will be based upon data from Part 1 and previous studies.

Participants in Part 3 of the study will be split into 2 cohorts. Each cohort will be administered, in the fasted state, a single dose of the tablet selected as optimal from previous study parts. The dose used will be based upon data from Parts 1 and 2 and previous studies.

Part 1 will assess the relative bioavailability of TAK-020 by using analysis of variance (ANOVA) on tmax, and the natural logarithms of AUCs, and Cmax. Part 2 will assess the food effect of TAK-020, also using ANOVA on tmax, and the natural logarithms of AUCs, and Cmax. The power model will be used to assess dose proportionality of single doses of the solid formulations in the fasted state from Parts 2 and 3.

Eligibility criteria: Inclusion Criteria:

1. Is capable of understanding and complying with protocol requirements.
2. Is legally acceptable representative 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 participant fast for any laboratory evaluations.
3. Is a healthy adult male or female.
4. Is aged 18 to 55 years, inclusive, at the time of informed consent and first study medication dose.
5. Weighs at least 45 kilogram (kg) and has a body mass index (BMI) between 18 and 32 kilogram per square meter (kg/m\^2), inclusive at Screening and Day -1.
6. 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 90 days after last dose of study medication.
7. 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 until the next menstrual period or 90 days after exit from the study, whichever is first. If the next menstrual period is delayed, a pregnancy test will be required for exclusion of pregnancy.

Exclusion Criteria:

1. Has received any investigational compound within 30 days prior to Screening.
2. 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.
3. Has a known hypersensitivity to any component of the formulation of TAK-020, Captisol, or related compounds.
4. Has a positive urine drug result for drugs of abuse or a positive breath alcohol screen at Screening or Check-in (Day -1).
5. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse (defined as 4 or more alcoholic units per day) within 1 year prior to the Screening visit or is unwilling to agree to abstain from alcohol and drugs throughout the study.
6. Has taken any excluded medication, supplements, or food products listed in Prohibited Medications and Foods table.
7. If female, is pregnant or lactating or intending to become pregnant before, during or within 3 months after exit from this study (90 days post last dose); or intending to donate ova during such time period.
8. If male, the participant intends to donate sperm during the course of this study or for 90 days after the last dose of study drug.
9. Has evidence of current cardiovascular, central nervous system, hepatic, hematopoietic disease, renal dysfunction, metabolic or endocrine dysfunction, serious allergy, asthma hypoxemia, hypertension, seizures, or allergic skin rash.
10. Has current or recent (within 6 months) gastrointestinal disease that would be expected to influence the absorption of drugs (that is, a history of malabsorption, esophageal reflux, peptic ulcer disease, erosive esophagitis, frequent \[more than once per week\] occurrence of heartburn, or any surgical intervention \[example, cholecystectomy\]).
11. Has a history of cancer, except basal cell carcinoma which has been in remission for at least 5 years prior to Day 1.
12. Has used nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patch or nicotine gum) within 28 days prior to Check-in Day -1. Cotinine test is positive at Screening or Check-in (Day -1).
13. Has poor peripheral venous access.
14. Has donated or lost 450 mililiter (mL) or more of his or her blood volume (including plasmapheresis), or had a transfusion of any blood product within 30 days prior to Day 1.
15. Has a Screening or Check-in (Day -1) 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 medically qualified subinvestigator.
16. Has QT interval with Fridericia correction method (QTcF) greater than (\>) 430 millisecond (msec) for men and \>450 msec for women or PR outside the range of 120 to 220 msec confirmed upon repeat testing within a maximum of 30 minutes, at the Screening Visit or Check-in (Day -1).
17. Has abnormal Screening or Day -1 laboratory values that suggest a clinically significant underlying disease or participant with the following lab abnormalities:

    1. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \>1.2\* the upper limit of normal (ULN).
    2. Positive screen test for drugs of abuse.
    3. Positive blood screen for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV), or human immunodeficiency virus-1 or -2 antibodies (test done at Screening visit only).
    4. A positive test for tuberculosis (TB) (QuantiFERON) (test done at Screening Visit only).
18. Vaccination with any live vaccine within 4 weeks of study drug administration.

Primary outcomes:
measure: Cmax: Maximum Observed Plasma Concentration for TAK-020
timeFrame: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose
measure: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-020
timeFrame: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose
measure: AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-020
timeFrame: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose
measure: Terminal Disposition Phase Half-life (T1/2z) in Plasma for TAK-020
timeFrame: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose
Secondary outcomes:
measure: Number of Participants Who Experience at Least One or More Treatment-emergent Adverse Event (TEAE)
timeFrame: Baseline up to 30 days after last dose of study drug (Day 58 in Part 1), (Day 40 in Part 2)
measure: Number of Participants Who Meet the Takeda Markedly Abnormal Criteria for Clinical Laboratory Tests at Least Once Post Dose
timeFrame: Baseline up to Day 2
measure: Number of Participants Who Meet the Takeda Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose
timeFrame: Baseline up to Day 2
measure: Number of Participants Who Meet the Takeda Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose
timeFrame: Baseline up to Day 2
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References: