Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of MLN3126 in Healthy Japanese and Non-Japanese Participants

NCT02209506 | Terminated Phase 1 Results

• 2 other identifiers: MLN3126_103U1111-1156-8528
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of single and multiple oral dosing of MLN3126 in ascending doses in healthy non-Japanese and Japanese participants.

Conditions

Safety; Tolerability; Pharmacokinetics; Pharmacodynamics

Keywords

MLN3126

Outcome Measures

Primary Outcomes (4)

• Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)

  A TEAE is defined as an adverse event with an onset that occurs after receiving study drug.

  Baseline up to 7 days after last dose of study drug (Day 22)

• Percentage of Participants Who Meet the Markedly Abnormal Criteria for Electrocardiogram Measurements at Least Once Post Dose

  A standard 12-lead ECG was performed. The percentage of participants with markedly abnormal electrocardiogram (ECG) findings during the study.

  Baseline up to 7 days after last dose of study drug (Day 22)

• Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose

  The percentage of participants with any markedly abnormal, according to Takeda criteria, standard safety laboratory values, including hematology, serum chemistry, and urinalysis, during the treatment period.

  Baseline up to 7 days after last dose of study drug (Day 22)

• Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose

  The percentage of participants who meet markedly abnormal criteria designated by Takeda Global Research and Development Center, Inc. (TGRD). Criteria for markedly abnormal vital signs included body temperature, systolic blood pressure, diastolic blood pressure and pulse rate.

  Baseline up to 7 days after last dose of study drug (Day 22)

Secondary Outcomes (16)

• Cmax: Maximum Plasma Concentration for MLN3126 and Its Metabolite

  Days 1 and 15: pre-dose and at multiple timepoints (up to 96 hours) post-dose

• Tmax- Time to Reach the Cmax for MLN3126 and Its Metabolite

  Days 1 and 15: pre-dose and at multiple timepoints (up to 96 hours) post-dose

• AUC(0-tau): Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau for MLN3126 and Its Metabolite

  Days 1 and 15: pre-dose and at multiple timepoints (up to 96 hours) post-dose

• AUC (0-last): Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for MLN3126 and Its Metabolite

  Days 1 and 15: pre-dose and at multiple timepoints (up to 96 hours) post-dose

• AUC(0-96): Area Under the Plasma Concentration-time Curve From Time 0 to 96 Hours Post Dose for MLN3126 and Its Metabolite

  Days 1 and 15: pre-dose and at multiple timepoints (up to 96 hours) post-dose

Study Arms (10)

Cohort 1A: MLN3126 100 mg Non-Japanese Participants

EXPERIMENTAL

MLN3126 100 mg, administered orally as tablets once on Day 1, followed by a 7 day washout period, followed by once daily administration for 7 days (Days 9 through 15) in healthy, non-Japanese participants.

Drug: MLN3126

Cohort 2A: MLN3126 300 mg Non-Japanese Participants

EXPERIMENTAL

MLN3126 300 mg, administered orally as tablets, orally, once on Day 1, followed by a 7 day washout period, followed by once daily administration for 7 days (Days 9 through 15) in healthy, non-Japanese participants.

Drug: MLN3126

Cohort 3A: MLN3126 800 mg Non-Japanese Participants

EXPERIMENTAL

MLN3126 800 mg, administered orally as tablets once on Day 1, followed by a 7 day washout period, followed by once daily administration for 7 days (Days 9 through 15) in healthy, non-Japanese participants.

Drug: MLN3126

Cohort 4A: MLN3126 TBD Non-Japanese Participants

EXPERIMENTAL

The MLN3126 dose for this Cohort will be determined based on data collected from Cohort 3A. MLN3126, tablets, administered orally, once on Day 1, followed by a 7 day washout period, followed by once daily administration for 7 days (Days 9 through 15) in healthy, non-Japanese participants.

Drug: MLN3126

Cohorts 1A - 4A: Matched Placebo Non-Japanese Participants

EXPERIMENTAL

MLN3126 placebo-matching tablets, administered orally, once on Day 1, followed by a 7 day washout period, followed by once daily administration for 7 days (Days 9 through 15) in healthy, non-Japanese participants.

Drug: MLN3126 Matched Placebo

Cohort 1B: MLN3126 100 mg Japanese Participants

EXPERIMENTAL

MLN3126 100 mg, administered orally as tablets, once on Day 1, followed by a 7 day washout period, followed by once daily administration for 7 days (Days 9 though 15) in healthy, Japanese participants.

Drug: MLN3126

Cohort 2B: MLN3126 300 mg Japanese Participants

EXPERIMENTAL

MLN3126 300 mg, administered orally as tablets, once on Day 1, followed by a 7 day washout period, followed by once daily administration for 7 days (Days 9 through 15) in healthy, Japanese participants.

Drug: MLN3126

Cohort 3B: MLN3126 800 mg Japanese Participants

EXPERIMENTAL

MLN3126 800 mg, tablets, orally, once on Day 1, followed by a 7 day washout period, followed by MLN3126 800 mg, tablets, orally, once daily for 7 days (Days 9 through 15) in healthy, Japanese participants.

Drug: MLN3126

Cohort 4B: MLN3126 TBD Japanese Participants

EXPERIMENTAL

The MLN3126 dose for this Cohort will be determined based on data collected from Cohort 3B. MLN3126, tablets, administered orally, once on Day 1, followed by a 7 day washout period, followed by once daily administration for 7 days (Days 9 through 15) in healthy, Japanese participants.

Drug: MLN3126

Cohorts 1B - 4B: Matched Placebo Japanese Participants

EXPERIMENTAL

MLN3126 placebo-matching tablets, administered orally, once on Day 1, followed by a 7 day washout period, followed by once daily for 7 days (Days 9 through 15) in healthy, Japanese participants.

Drug: MLN3126 Matched Placebo

Interventions

MLN3126 DRUG

MLN3126 tablets

Cohort 1A: MLN3126 100 mg Non-Japanese Participants; Cohort 1B: MLN3126 100 mg Japanese Participants; Cohort 2A: MLN3126 300 mg Non-Japanese Participants; Cohort 2B: MLN3126 300 mg Japanese Participants; Cohort 3A: MLN3126 800 mg Non-Japanese Participants; Cohort 3B: MLN3126 800 mg Japanese Participants; Cohort 4A: MLN3126 TBD Non-Japanese Participants; Cohort 4B: MLN3126 TBD Japanese Participants

MLN3126 Matched Placebo DRUG

MLN3126 placebo-matching tablets

Cohorts 1A - 4A: Matched Placebo Non-Japanese Participants; Cohorts 1B - 4B: Matched Placebo Japanese Participants

Eligibility Criteria

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

You may qualify if:

• Part A (Healthy non-Japanese participants):
• In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
• The 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.
• Is a male or female adult, 18 to 55 years of age, inclusive, at the time of informed consent and study drug dosing.
• Is a healthy adult male or female participant as evidenced by their medical history, complete physical examination, vital signs, electrocardiogram (ECG), and safety laboratory evaluations.
• Weighs at least 45 kg and has a body mass index (BMI) between 18 and 30 kg/m\^2 inclusive at Screening.
• 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.
• A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to routinely use adequate contraception from signing of informed consent throughout the duration of the study to their next postconfinement menstruation. In addition, participants must be advised not to donate ova during this period.
• Part B (Healthy Japanese participants):
• In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
• The 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.
• Is a male or female adult, 20 to 55 years of age, inclusive, at the time of informed consent and study drug dosing, is of Japanese descent (born to Japanese parents and grandparents and has lived outside Japan for less than 15 years), and maintains a Japanese diet and lifestyle.
• Is a healthy adult male or female participant as evidenced by their medical history, complete physical examination, vital signs, ECG, and safety laboratory evaluations.
• Weighs at least 45 kg and has a BMI between 18 and 28 kg/m\^2 inclusive at Screening.
• 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 the last dose.

You may not qualify if:

• Part A (Healthy non-Japanese participants) and Part B (Healthy Japanese participants):
• Has received any investigational compound within 30 days or 5 half-lives of the investigational compound, whichever is longer, prior to the first dose of study medication.
• Has received MLN3126 in a previous clinical study.
• Is an immediate family member, study site employee, or in a dependant relationship with a study site employee who is involved in the conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.
• Has uncontrolled, clinically significant neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal (GI), or endocrine disease or allergic skin rash or other abnormality which may impact the ability of the participant to participate or potentially confound the study results.
• Has a known hypersensitivity to any component of the formulation of MLN3126.
• Has a positive urine drug result for drugs of abuse at Screening or Check-in (Day -1).
• 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.
• Has taken any excluded medication, supplements, or food products listed in the Excluded Medications and Dietary Products section of the protocol.
• If female, the participant is pregnant or lactating or intending to become pregnant before or during the study, including the timeframe to the participant's next post-confinement menstruation after participating in this study.
• If male, the participant intends to donate sperm during the course of this study or for 12 weeks thereafter.
• Has current or recent (within 6 months) GI disease that would be expected to influence the absorption of drugs (ie, a history of malabsorption, any surgical intervention known to impact absorption \[eg, bariatric surgery or bowel resection\], esophageal reflux, peptic ulcer disease, erosive esophagitis, or frequent \[more than once per week\] occurrence of heartburn).
• Has Gilbert's syndrome or bilirubin level 1.2x the upper limits of normal (ULN).
• Has a history of cancer, except basal cell carcinoma, that has been in remission for at least 5 years prior to Day 1.
• Has a positive test result for hepatitis B surface antigen (HBsAg) or antibody to hepatitis C virus (anti-HCV) at Screening or a known history of human immunodeficiency virus infection.

Sponsors & Collaborators

• Takeda: lead

Study Sites (1)

Unknown Facility

Neptune City, New Jersey, 07753, 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: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2014
• First Posted: August 6, 2014
• Study Start: July 1, 2014
• Primary Completion: September 1, 2014
• Study Completion: December 1, 2014
• Last Updated: July 25, 2016
• Results First Posted: July 25, 2016

Record last verified: 2016-07

Locations

US (1)