Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Ascending Single- and Multiple-Doses of TAK-020 in Healthy Volunteers

NCT02413255 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: TAK-020-1001U1111-1163-9637
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of ascending single- and multiple-doses of TAK-020 in healthy participants.

Conditions

Healthy Volunteers

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (8)

• Percentage of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE) in Part 1 Single-rising Dose (SRD)

  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 TEAE is defined as an adverse event that occurred or worsened after receiving study drug.

  First dose of study drug up to and including 30 days after last dose of study drug (Up to 31 days) for Part 1

• Percentage of Participants With Markedly Abnormal Values (MAV) for Safety Laboratory Findings at Least Once Post-dose in Part 1 (SRD)

  Safety laboratory tests includes hematology, serum chemistries, and urinalysis.

  From Day 1 to Day 14 of Part 1

• Percentage of Participants With MAV for Vital Sign Measurements at Least Once Post-dose in Part 1 (SRD)

  Vital signs include oral temperature, respiratory rate, sitting blood pressure (after 5 minutes resting) and pulse beats per minute (bpm).

  From Day 1 to Day 14 of Part 1

• Percentage of Participants With MAV for Safety Electrocardiogram (ECG) Parameters at Least Once Post-dose in Part 1 (SRD)

  A standard 12-lead ECG was performed. Change from baseline=CFB.

  From Day 1 to Day 14 in Part 1

• Percentage of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE) in Part 2 Multiple-rising Dose (MRD)

  An 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 TEAE is defined as an adverse event that occurred or worsened after receiving study drug.

  First dose of study drug up to and including 30 days after last dose of study drug (Up to 39 days) in Part 2

• Percentage of Participants With MAV for Safety Laboratory Findings at Least Once Post-dose in Part 2 (MRD)

  Safety laboratory tests include hematology, and serum chemistries.

  From Day 1 to Day 17 in Part 2

• Percentage of Participants With MAV for Vital Sign Measurements at Least Once Post-dose in Part 2 (MRD)

  Vital signs include oral temperature respiratory rate, sitting blood pressure (after 5 minutes resting) and pulse (bpm).

  From Day 1 to Day 17 in Part 2

• Percentage of Participants With MAV for Safety ECG Parameters at Least Once Post-dose in Part 2 (MRD)

  A standard 12-lead ECG was performed.

  From Day 1 to Day 17 in Part 2

Secondary Outcomes (35)

• Cmax: Maximum Observed Plasma Concentration for TAK-020 in Part 1 (SRD)

  Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1

• Cmax: Maximum Observed Plasma Concentration for TAK-020 in Part 2 (MRD)

  Pre-dose and multiple timepoints (up to 48 hours) post-dose on Day 1 and pre-dose and multiple timepoints (up to 24 hours) post-dose on Day 9 in Part 2

• Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-020 in Part 1 (SRD)

  Pre-dose and multiple timepoints (up to 96 hours) post-dose in Part 1

• Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-020 in Part 2 (MRD)

  Pre-dose and multiple timepoints (up to 48 hours) post-dose on Day 1 and pre-dose and multiple time-points (up to 24 hours) post dose on Day 9 in Part 2

• AUC24: Area Under the Plasma Concentration-time Curve From Time 0 to Time 24 Hours for TAK-020 in Part 1 (SRD)

  Pre-dose and multiple timepoints (up to 24 hours) post-dose in Part 1

Study Arms (17)

Part 1 Cohort 1-9: Placebo

PLACEBO COMPARATOR

TAK-020 placebo-matching solution, orally, once on Day 1.

Drug: TAK-020 Placebo

Part 1 Cohort 1: TAK-020 0.1 mg

EXPERIMENTAL

TAK-020 0.1 mg, solution, orally once on Day 1.

Drug: TAK-020

Part 1 Cohort 2: TAK-020 0.5 mg

EXPERIMENTAL

TAK-020 0.5 mg, solution, orally, once on Day 1 following review of safety, tolerability and pharmacokinetic (PK) data from Cohort 1.

Drug: TAK-020

Part 1 Cohort 3: TAK-020 2.5 mg

EXPERIMENTAL

TAK-020 2.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 2.

Drug: TAK-020

Part 1 Cohort 4: TAK-020 4.4 mg

EXPERIMENTAL

TAK-020 4.4 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 3.

Drug: TAK-020

Part 1 Cohort 5: TAK-020 8.8 mg

EXPERIMENTAL

TAK-020 8.8 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 4.

Drug: TAK-020

Part 1 Cohort 6: TAK-020 17.5 mg

EXPERIMENTAL

TAK-020 17.5 mg, solution, orally once on Day 1 following review of safety, tolerability and PK data from Cohort 5.

Drug: TAK-020

Part 1 Cohort 7: TAK-020 35 mg

EXPERIMENTAL

TAK-020 35 mg, solution, orally once on Day 1. TAK-020 dose will be determined based on review of safety, tolerability and PK data from Cohort 6.

Drug: TAK-020

Part 1 Cohort 8: TAK-020 70 mg

EXPERIMENTAL

TAK-020 70 mg, solution, orally once on Day 1. TAK-020 dose will be determined based on review of safety, tolerability and PK data from Cohort 7.

Drug: TAK-020

Part 1 Cohort 9: TAK-020 105 mg

EXPERIMENTAL

TAK-020 105 mg, solution, orally once on Day 1. TAK-020 dose will be determined based on review of safety, tolerability and PK data from Cohort 8.

Drug: TAK-020

Part 2 Cohort 1-6: Placebo

PLACEBO COMPARATOR

TAK-020 placebo-matching solution, orally, once on Day 1 and Days 3 to 9.

Drug: TAK-020 Placebo

Part 2 Cohort 1: TAK-020 3.75 mg

EXPERIMENTAL

TAK-020 3.75 mg, solution, orally once on Day 1 and Days 3-9. TAK-020 dose are determined based on data from Part 1 of the study.

Drug: TAK-020

Part 2 Cohort 2: TAK-020 5.75 mg

EXPERIMENTAL

TAK-020 5.75 mg, solution, orally once on Day 1 and Days 3-9. TAK-020 dose will be determined based on data from Part 1 and review of safety, tolerability and PK data from Cohort 1 in Part 2.

Drug: TAK-020

Part 2 Cohort 3: TAK-020 13 mg

EXPERIMENTAL

TAK-020 13 mg, solution, orally once on Day 1 and Days 3-9. TAK-020 dose will be determined based on data from Part 1 and review of safety, tolerability and PK data from Cohort 2 in Part 2.

Drug: TAK-020

Part 2 Cohort 4: TAK-020 25 mg

EXPERIMENTAL

TAK-020 25 mg, solution, orally once on Day 1 and Days 3-9. TAK-020 dose will be determined based on data from Part 1 and review of safety, tolerability and PK data from Cohort 3 in Part 2.

Drug: TAK-020

Part 2 Cohort 5: TAK-020 45 mg

EXPERIMENTAL

TAK-020 45 mg, solution, orally once on Day 1 and Days 3-9. TAK-020 dose was determined based on data from Part 1 and review of safety, tolerability and PK data from Cohort 4 in Part 2.

Drug: TAK-020

Part 2 Cohort 6: TAK-020 60 mg

EXPERIMENTAL

TAK-020 60 mg, solution, orally once on Day 1 and Days 3-9. TAK-020 dose was determined based on data from Part 1 and review of safety, tolerability and PK data from Cohort 5 in Part 2.

Drug: TAK-020

Interventions

TAK-020 DRUG

TAK-020 oral solution

Part 1 Cohort 1: TAK-020 0.1 mg; Part 1 Cohort 2: TAK-020 0.5 mg; Part 1 Cohort 3: TAK-020 2.5 mg; Part 1 Cohort 4: TAK-020 4.4 mg; Part 1 Cohort 5: TAK-020 8.8 mg; Part 1 Cohort 6: TAK-020 17.5 mg; Part 1 Cohort 7: TAK-020 35 mg; Part 1 Cohort 8: TAK-020 70 mg; Part 1 Cohort 9: TAK-020 105 mg; Part 2 Cohort 1: TAK-020 3.75 mg; Part 2 Cohort 2: TAK-020 5.75 mg; Part 2 Cohort 3: TAK-020 13 mg; Part 2 Cohort 4: TAK-020 25 mg; Part 2 Cohort 5: TAK-020 45 mg; Part 2 Cohort 6: TAK-020 60 mg

TAK-020 Placebo DRUG

TAK-020 placebo-matching oral solution

Part 1 Cohort 1-9: Placebo; Part 2 Cohort 1-6: Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participant eligibility is determined according to the following criteria prior to entry into the study:
• In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
• Participant or, when applicable, the participant's 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.
• Participant is a healthy adult male or female.
• The participant is a health adult male or female aged 18 to 55 years, inclusive, at the time of informed consent and first study medication dose.
• The participant weighs at least 45 kilogram (kg) and has a body mass index (BMI) between 18.0 and 32.0 kilogram per square meter (kg/m\^2), inclusive at Screening and Day -1.
• A 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.

You may not qualify if:

• Any participant who meets any of the following criteria will not qualify for entry into the study:
• The participant has received any investigational compound within 30 days prior to Screening.
• The participant is an immediate family member, study site employee, or 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.
• Participant has a known hypersensitivity to any component of the formulation of TAK-020, Captisol or related compounds.
• The participant has a positive urine drug result for drugs of abuse at Screening or Check-in (Day -1).
• The participant has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse (defined as 4 or more alcoholic beverages per day) within 1 year 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 1 measure of spirits or 1 glass of wine.
• Participant has taken any excluded medication, supplements, or food products, Prohibited Medications and Dietary Products.
• If female, the participant is pregnant or lactating or intending to become pregnant before, during or within 1 month after exit from this study (30 days post last dose); or intending to donate ova during such time period.
• If male, the participant intends to donate sperm during the course of this study or for 12 weeks thereafter.
• Participant 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. There is any finding in the participant's medical history, physical examination, or safety laboratory tests giving reasonable suspicion of a disease that would contraindicate taking TAK-020, or a similar drug in the same class, or that might interfere with the conduct of the study. This includes, but is not limited to, peptic ulcer disease, seizure disorders, and cardiac arrhythmias.
• Participant 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 \[example, cholecystectomy\]).
• Participant has a history of cancer, except basal cell carcinoma which has been in remission for at least 5 years prior to Day 1.
• Participant 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).
• The participant has poor peripheral venous access.
• Participant has donated or lost 450 milliliter (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.

Sponsors & Collaborators

• Takeda: lead

Study Sites (1)

Unknown Facility

Glendale, California, United States

Location

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director Clinical Science

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 6, 2015
• First Posted: April 9, 2015
• Study Start: March 18, 2015
• Primary Completion: May 4, 2017
• Study Completion: May 4, 2017
• Last Updated: January 7, 2019
• Results First Posted: January 7, 2019

Record last verified: 2018-06

Locations

US (1)