MLN3126 Single Rising Dose Study
Condition: Healthy Volunteers
Intervention: MLN3126; MLN3126 Placebo
Intervention description: MLN3126 tablets; MLN3126 placebo-matching tablets
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 39.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Drug therapy

Summary:

      The purpose of this study was to evaluate the safety, tolerability, and pharmacokinetics of
      MLN3126 when administered as a single dose of tablets at escalating dose levels in healthy
      participants.
    

Eligibility criteria:

        Inclusion Criteria:

          1. In the opinion of the investigator, the participant was capable of understanding and
             complying with protocol requirements.

          2. The participant or, when applicable, the participant's legally acceptable
             representative signed and dated a written, informed consent form and any required
             privacy authorization prior to the initiation of any study procedures.

          3. Is a male or female adult, aged 18 to 55 years, inclusive, at the time of informed
             consent and study drug dosing.

          4. Is a healthy adult male or female subject as evidenced by their medical history,
             complete physical examination, vital signs, ECG, and safety laboratory evaluations.

          5. Weighed at least 45 kg (99 lbs) and had a body mass index (BMI) between 18 and 30.0
             kg/m2 inclusive at Screening.

          6. A male participant who was nonsterilized and sexually active with a female partner of
             childbearing potential agreed to use adequate contraception from signing of informed
             consent throughout the duration of the study and for 12 weeks after last dose. In
             addition, participants were advised not to donate sperm during this period.

          7. A female participant of childbearing potential who was sexually active with a
             nonsterilized male partner agreed to use routinely adequate contraception from signing
             of informed consent throughout the duration of the study to their next postconfinement
             menstruation. In addition participants were advised not to donate ova during this
             period.

        Exclusion Criteria:

        Any participant who meets any of the following criteria will not qualify for entry into the
        study:

          1. Has received any investigational compound within 30 days prior to the first dose of
             study medication.

          2. 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 (eg, spouse,
             parent, child, sibling) or may consent under duress.

          3. Has uncontrolled, clinically significant neurologic, cardiovascular, pulmonary,
             hepatic, renal, metabolic, GI, or endocrine disease or other abnormality, which may
             impact the ability of the participant to participate or potentially confound the study
             results.

          4. Has a known hypersensitivity to any component of the formulation of MLN3126.

          5. Has a positive urine drug result for drugs of abuse at Screening or Check-in (Day -1).

          6. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol
             abuse (defined as 4 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.

          7. Has taken any excluded medication, supplements, or food products listed in the
             Excluded Medications and Dietary Products section of the protocol.

          8. If female, the participant is pregnant or lactating or intending to become pregnant,
             or intending to donate ova, before or during, the study; including the timeframe to
             participant's next postconfinement menstruation after participating in this study.

          9. If male, the participant intends to donate sperm during the course of this study or
             for 12 weeks thereafter.

         10. 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 contra indicate taking MLN3126 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.

         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 a history of cancer or other malignancy, except basal cell carcinoma that has been
             in remission for at least 5 years prior to Day 1.

         13. Has a positive test result for hepatitis B surface antigen, antibody to hepatitis C
             virus, at Screening or a known history of human immunodeficiency virus infection.

         14. Has used nicotine-containing products (this includes, but is 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).

         15. Has poor peripheral venous access.

         16. 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.

         17. Has a Screening or Check-in (Day -1) abnormal (clinically significant) ECG. Entry of
             any subject with an abnormal (not clinically significant) ECG must be approved, and
             documented by signature by the principal investigator or medically qualified
             subinvestigator.

         18. 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.

         19. Has QT interval with Fridericia correction method (QTcF) >430 ms for men and >450 ms
             for women or PR outside the range of 120 to 220 ms confirmed upon repeat testing
             within a maximum of 5 minutes, at the Screening Visit or Check-in (Day -1).