Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of MLN3126 in Healthy Japanese and Non-Japanese Participants
Condition: Safety; Tolerability; Pharmacokinetics; Pharmacodynamics
Intervention: MLN3126; MLN3126 Matched Placebo
Intervention description: MLN3126 tablets; MLN3126 placebo-matching tablets
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 23.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: MLN3126

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.
    

Eligibility criteria:

        Inclusion Criteria:

        Part A (Healthy non-Japanese participants):

          1. In the opinion of the investigator, the participant is capable of understanding and
             complying with protocol requirements.

          2. 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.

          3. Is a male or female adult, 18 to 55 years of age, inclusive, at the time of informed
             consent and study drug dosing.

          4. 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.

          5. Weighs at least 45 kg and has a body mass index (BMI) between 18 and 30 kg/m^2
             inclusive at Screening.

          6. 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.

          7. 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):

          1. In the opinion of the investigator, the participant is capable of understanding and
             complying with protocol requirements.

          2. 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.

          3. 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.

          4. Is a healthy adult male or female participant as evidenced by their medical history,
             complete physical examination, vital signs, ECG, and safety laboratory evaluations.

          5. Weighs at least 45 kg and has a BMI between 18 and 28 kg/m^2 inclusive at Screening.

          6. 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.

          7. 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.

        Exclusion Criteria:

        Part A (Healthy non-Japanese participants) and Part B (Healthy Japanese participants):

          1. 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.

          2. Has received MLN3126 in a previous clinical study.

          3. 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.

          4. 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.

          5. Has a known hypersensitivity to any component of the formulation of MLN3126.

          6. Has a positive urine drug result for drugs of abuse at Screening or Check-in (Day -1).

          7. 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.

          8. Has taken any excluded medication, supplements, or food products listed in the
             Excluded Medications and Dietary Products section of the protocol.

          9. 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.

         10. If male, the participant intends to donate sperm during the course of this study or
             for 12 weeks thereafter.

         11. 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).

         12. Has Gilbert's syndrome or bilirubin level 1.2x the upper limits of normal (ULN).

         13. Has a history of cancer, except basal cell carcinoma, that has been in remission for
             at least 5 years prior to Day 1.

         14. 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.

         15. 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).

         16. Has poor peripheral venous access.

         17. Has donated or lost 450 mL or more of his or her blood volume (including
             plasmapheresis) or had a transfusion of any blood product within 45 days prior to Day
             1.

         18. Has a Screening or Check-in (Day -1) abnormal (clinically significant)
             electrocardiogram (ECG). Entry of any participant with an abnormal (not clinically
             significant) ECG must be approved, and documented by signature by the principal
             investigator.

         19. Has a QT interval with Fridericia correction method (QTcF) > 430 milliseconds (ms) for
             men or > 450 ms for women or a PR outside the range of 120 to 210 ms confirmed upon
             repeat testing within a maximum of 30 minutes, at the Screening Visit or Check-in (Day
             -1).

         20. Has abnormal Screening or Check-in (Day -1) laboratory values that suggest a
             clinically significant underlying disease or participant with the following laboratory
             abnormalities: Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST)
             > 1.5 ULN.