MLN3126 Single Rising Dose Study

NCT02447458 | Terminated Phase 1 Results

• 2 other identifiers: MLN3126_102U1111-1163-1717
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy Volunteers

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (4)

• Number of Participants That Experience At Least One Treatment-Emergent Adverse Event (TEAE) Post-Dose

  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. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.

  Up to Day 22

• Percentage of Participants With Markedly Abnormal Clinical Laboratory Results Post-Dose

  Clinical safety laboratory tests included clinical chemistry, hematology and urinalysis. The percentage of participants with any markedly abnormal laboratory finding during the study.

  Up to Day 16

• Percentage of Participants With Markedly Abnormal Vital Signs Post-Dose

  Vital signs included oral body temperature measurement, blood pressure, respiration rate, and pulse rate \[beats per minute (bpm) or heart rate\]. The percentage of participant with markedly abnormal vital signs findings during the study. OBP=Orthostatic Blood Pressure. All OBP measurements were standing.

  Up to Day 16

• Percentage of Participants With Markedly Abnormal Electrocardiogram (ECG) Findings Post-Dose

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

  Up to Day 16

Secondary Outcomes (9)

• Cmax: Maximum Plasma Concentration of MLN3126 and Metabolite M-I

  Pre-dose and multiple timepoints post-dose (Up to 96 Hours)

• Tmax: Time to Maximum Plasma Concentration of MLN3126 and Metabolite M-I

  Pre-dose and multiple timepoints post-dose (Up to 96 Hours)

• AUC(0-tlqc): Area Under the Plasma Concentration Time Curve of MLN3126 and Metabolite M-I From Time 0 to the Last Quantifiable Concentration

  Pre-dose and multiple timepoints post-dose (Up to 96 Hours)

• AUC(0-inf): Area Under the Plasma Concentration Time Curve of MLN3126 and Metabolite M-I From Time 0 to Infinity

  Pre-dose and multiple timepoints post-dose (Up to 96 Hours)

• CL/F: Oral Clearance of MLN3126

  Pre-dose and multiple timepoints post-dose (Up to 96 Hours)

Study Arms (7)

Cohort 1: MLN3126 300 mg

EXPERIMENTAL

MLN3126 300 mg tablets, orally, fasting, once on Day 1.

Drug: MLN3126

Cohort 2: MLN3126 600 mg

EXPERIMENTAL

MLN3126 600 mg tablets, orally, fasting, once on Day 1.

Drug: MLN3126

Cohort 3: MLN3126 1000 mg

EXPERIMENTAL

MLN3126 1000 mg tablets, orally, fasting, once on Day 1. Participants returned to the clinic then received MLN3126 1000 mg tablets, orally, fed (30 minutes after the start of a high-fat breakfast), once on Day 1.

Drug: MLN3126

Cohort 4: MLN3126 1500 mg

EXPERIMENTAL

MLN3126 1500 mg administered orally as tablets, once on Day 1.

Drug: MLN3126

Cohort 5: MLN3126 2000 mg

EXPERIMENTAL

MLN3126 2000 mg tablets, orally, fasting, once on Day 1.

Drug: MLN3126

Cohort 6

EXPERIMENTAL

Did not take place due to termination of the study.

Drug: MLN3126

Placebo: Cohort 1-6

PLACEBO COMPARATOR

Placebo-matching MLN3126 tablets, orally, once on Day 1.

Drug: MLN3126 Placebo

Interventions

MLN3126 DRUG

MLN3126 tablets

Cohort 1: MLN3126 300 mg; Cohort 2: MLN3126 600 mg; Cohort 3: MLN3126 1000 mg; Cohort 4: MLN3126 1500 mg; Cohort 5: MLN3126 2000 mg; Cohort 6

MLN3126 Placebo DRUG

MLN3126 placebo-matching tablets

Placebo: Cohort 1-6

Eligibility Criteria

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

You may qualify if:

• In the opinion of the investigator, the participant was capable of understanding and complying with protocol requirements.
• 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.
• Is a male or female adult, aged 18 to 55 years, inclusive, at the time of informed consent and study drug dosing.
• Is a healthy adult male or female subject as evidenced by their medical history, complete physical examination, vital signs, ECG, and safety laboratory evaluations.
• Weighed at least 45 kg (99 lbs) and had a body mass index (BMI) between 18 and 30.0 kg/m2 inclusive at Screening.
• 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.
• 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.

You may not qualify if:

• Any participant who meets any of the following criteria will not qualify for entry into the study:
• Has received any investigational compound within 30 days prior to the first dose of study medication.
• 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.
• 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.
• 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 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, or intending to donate ova, before or during, the study; including the timeframe to participant's next postconfinement 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 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.
• 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 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.
• 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.
• 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).

Sponsors & Collaborators

• Takeda: lead

Study Sites (1)

Unknown Facility

Eatontown, New Jersey, United States

Location

Results Point of Contact

• Title: Takeda Study Registration Call Center
• Organization: Takeda

medicalinformation@tpna.com

+1-877-825-3327

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: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2015
• First Posted: May 18, 2015
• Study Start: September 1, 2013
• Primary Completion: January 1, 2014
• Study Completion: February 1, 2014
• Last Updated: August 5, 2015
• Results First Posted: August 5, 2015

Record last verified: 2015-07

Locations

US (1)