Phase 1, TAK-915-1001, Single-Rising Dose, Multiple-Rising Dose, Drug-Drug Interaction, Relative Bioavailability, Food Effect, and Effect on Elderly Participants Study

NCT02461160 | Completed Phase 1 Results

• 2 other identifiers: TAK-915-1001U1111-1168-6456
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to characterize the safety, tolerability and plasma pharmacokinetic (PK) profile of TAK-915 when administered as single and multiple oral suspension doses at escalating dose levels in healthy participants, including elderly participants.

Conditions

Healthy Volunteers

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (15)

• Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE)

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

  Day 1 up to follow-up (SRD Cohorts: up to Day 13, MRD Cohorts: up to Day 26, DDI Cohort: up to Day 28, BA/FE Cohorts: up to Day 13, ESSD Cohort: up to Day 28)

• Percentage of Participants With Markedly Abnormal Safety Laboratory Tests

  The percentage of participants with any markedly abnormal standard safety laboratory values, including haematology, serum chemistries, or urinalysis, during the treatment period.

  Day 1 up to follow-up (SRD Cohorts: up to Day 13, MRD Cohorts: up to Day 26, DDI Cohort: up to Day 28, BA/FE Cohorts: up to Day 13, ESSD Cohort: up to Day 28)

• Percentage of Participants With Markedly Abnormal Vital Sign Measurements

  The percentage of participants who meet markedly abnormal criteria for vital signs after dosing, including oral body temperature (temp.), respiration rate, pulse rate (PR) Systolic blood pressure (SBP) and Diastolic blood pressure (DBP) for assessment in positions of supine or standing. Vital signs were considered abnormal if they were beyond the values defined in categories.

  Day 1 up to follow-up (SRD Cohorts: up to Day 13, MRD Cohorts: up to Day 26, DDI Cohort: up to Day 28, BA/FE Cohorts: up to Day 13, ESSD Cohort: up to Day 28)

• Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters

  The percentage of participants who meet markedly abnormal criteria for ECG parameters as specified by the protocol and statistical analysis plan during the treatment period. ECG parameters were considered abnormal if they were beyond the values defined in categories.

  Day 1 up to follow-up (SRD Cohorts: up to Day 13, MRD Cohorts: up to Day 26, DDI Cohort: up to Day 28, BA/FE Cohorts: up to Day 13, ESSD Cohort: up to Day 28)

• Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-915

  SRD and ESSD Cohorts: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post dose; MRD cohorts: Days 1, 8 and 14 pre-dose and at multiple timepoints (up to 96 hours) post dose

• Cmax: Maximum Observed Plasma Concentration for TAK-915

  SRD and ESSD Cohorts: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post dose; MRD cohorts: Days 1, 8 and 14 pre-dose and at multiple timepoints (up to 96 hours) post dose

• AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-915

  SRD and ESSD Cohorts: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post dose; MRD cohorts: Days 1, 8 and 14 pre-dose and at multiple timepoints (up to 96 hours) post dose

• AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-915

  SRD and ESSD Cohorts: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post dose; MRD cohorts: Days 1, 8 and 14 pre-dose and at multiple timepoints (up to 96 hours) post dose

• AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-915

  Day 1 pre-dose and at multiple time points (up to 96 hours) post dose

• Rac(AUC): Accumulation Ratios Between Day 14 AUC(0-24) and Day 1 AUC(0-24) for TAK-915

  Days 1 and 14 pre-dose and at multiple time points (up to 96 hours) post dose

• Rac(Cmax): Accumulation Ratios Between Day 14 Cmax and Day 1 Cmax for TAK-915

  Days 1 and 14 pre-dose and at multiple time points (up to 96 hours) post dose

• Time Dependency Assessment From AUC(0-24) After Last Dose for TAK-915 on Day 14 in MRD Cohorts Compared to AUC(0-inf) After a Single Dose on Day 1

  Days 1 and 14 pre-dose and at multiple time points (up to 96 hours) post dose

• Cmax: Maximum Observed Plasma Concentration for Midazolam Alone (Day 1) and in the Presence of TAK-915 (Day 16) in DDI Cohort

  Days 1 and 16 pre-dose and at multiple timepoints (up to 24 hours) post dose

• AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for Midazolam Alone (Day 1) and in the Presence of TAK-915 (Day 16) in DDI Cohort

  Days 1 and 16 pre-dose and at multiple timepoints (up to 24 hours) post dose

• AUC(0-24) for Midazolam After Single Dose (Day 1)/AUC(0-24) for Midazolam After 7 Daily Doses of TAK-915 (Day 16) in DDI Cohort

  Days 1 and 16 pre-dose and at multiple timepoints (up to 24 hours) post dose

Secondary Outcomes (18)

• Terminal Elimination Half-life (t1/2) for TAK-915

  SRD and ESSD Cohorts: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post dose; MRD cohorts: Days 1 and 14 pre-dose and at multiple timepoints (up to 96 hours) post dose

• CL/F: Apparent Clearance for TAK-915

  SRD and ESSD Cohorts: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post dose; MRD cohorts: Days 1 and 14 pre-dose and at multiple timepoints (up to 96 hours) post dose

• Apparent Volume of Distribution (Vz/F) for TAK-915

  SRD and ESSD Cohorts: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post dose; MRD cohorts: Days 1 and 14 pre-dose and at multiple timepoints (up to 96 hours) post dose

• Total Amount of Drug Excreted in Urine (Ae) for TAK-915

  SRD Cohorts: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post dose; MRD cohorts: Days 1 and 14 pre-dose and at multiple timepoints (up to 96 hours) post dose

• Fraction of Drug Excreted in Urine (Fe) for TAK-915

  SRD Cohorts: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post dose; MRD cohorts: Days 1 and 14 pre-dose and at multiple timepoints (up to 96 hours) post dose

Study Arms (13)

SRD Cohorts 1-3: Placebo

PLACEBO COMPARATOR

TAK-915 placebo-matching suspension, orally, once on Day 1.

Drug: TAK-915 suspension

SRD Cohort 1 TAK-915 30 mg

EXPERIMENTAL

TAK-915 30 mg suspension, orally, once on Day 1.

Drug: TAK-915 suspension

SRD Cohort 2: TAK-915 100 mg

EXPERIMENTAL

TAK-915 100 mg suspension, orally, once on Day 1.

Drug: TAK-915 suspension

SRD Cohort 3: TAK-915 200 mg

EXPERIMENTAL

TAK-915 200 mg suspension, orally, once on Day 1.

Drug: TAK-915 suspension

MRD Cohorts 4-6

PLACEBO COMPARATOR

TAK-915 placebo-matching suspension, orally, once on Day 1, followed by a 7-day washout period, followed by TAK-915 placebo-matching suspension, orally, once on Days 8 to 14.

Drug: TAK-915 suspension

MRD Cohort 4: TAK-915 30 mg

EXPERIMENTAL

TAK-915 30 mg suspension, orally, once on Day 1, followed by a 7-day washout period, followed by TAK-915 30 mg suspension, orally, once on Days 8 to 14.

Drug: TAK-915 suspension

MRD Cohort 5: TAK-915 100 mg

EXPERIMENTAL

TAK-915 100 mg suspension, orally, once on Day 1, followed by a 7-day washout period, followed by TAK-915 100 mg suspension, orally, once on Days 8 to 14.

Drug: TAK-915 suspension

MRD Cohort 6: TAK-915 200 mg

EXPERIMENTAL

TAK-915 200 mg suspension, orally, once on Day 1, followed by a 7-day washout period, followed by TAK-915 200 mg suspension, orally, once on Days 8 to 14.

Drug: TAK-915 suspension

DDI Cohort 7: TAK-915 + Midazolam 2 mg

EXPERIMENTAL

Midazolam 2 mg suspension, orally, once on Day 1, followed by TAK-915 100 mg, suspension, orally, once on Day 3, followed by a 7-day washout period, followed by TAK-915 100 mg, suspension, orally, once, daily on Days 10 to 16 and Midazolam 2 mg solution, orally, once, on Day 16 (within 15 minutes after last dose of TAK-915).

Drug: TAK-915 suspension

BA/FE Cohort 8 Group 1: A,B,C

EXPERIMENTAL

Regimen A: TAK-915 50 mg, suspension, orally, under fasted conditions once on Day 1 of Period 1, followed by Regimen B: TAK-915 50 mg, tablet, orally, under fasted conditions once on Day 1 of Period 2, followed by Regimen C: TAK-915 50 mg, tablet, orally under fed conditions once on Day 1 of Period 3. Each period was separated out by a 6 to 14-day washout period.

Drug: TAK-915 suspension

BA/FE Cohort 9 Group 1: B,C,A

EXPERIMENTAL

Regimen B: TAK-915 50 mg, tablet, orally, under fasted conditions once on Day 1 of Period 2, followed by Regimen C: TAK-915 50 mg, tablet, orally under fed conditions once on Day 1 of Period 3 followed by Regimen A: TAK-915 50 mg, suspension, orally, under fasted conditions once on Day 1 of Period 1. Each period was separated out by a 6 to 14-day washout period.

Drug: TAK-915 suspension; Drug: Midazolam

BA/FE Cohort 10 Group 1: C,A,B

EXPERIMENTAL

Regimen C: TAK-915 50 mg, tablet, orally under fed conditions once on Day 1 of Period 3 followed by Regimen A: TAK-915 50 mg, suspension, orally, under fasted conditions once on Day 1 of Period 1 followed by Regimen B: TAK-915 50 mg, tablet, orally, under fasted conditions once on Day 1 of Period 2. Each period was separated out by a 6 to 14-day washout period.

Drug: Placebo

ESSD Cohort 11: TAK-915 50 mg

EXPERIMENTAL

TAK-915 50 mg, suspension, orally, under fasted conditions, once on Day 1 in participants aged 65 to 75 years.

Drug: TAK-915 suspension; Drug: TAK-915 tablet

Interventions

TAK-915 suspension DRUG

TAK-915 oral suspension

BA/FE Cohort 8 Group 1: A,B,C; BA/FE Cohort 9 Group 1: B,C,A; DDI Cohort 7: TAK-915 + Midazolam 2 mg; ESSD Cohort 11: TAK-915 50 mg; MRD Cohort 4: TAK-915 30 mg; MRD Cohort 5: TAK-915 100 mg; MRD Cohort 6: TAK-915 200 mg; MRD Cohorts 4-6; SRD Cohort 1 TAK-915 30 mg; SRD Cohort 2: TAK-915 100 mg; SRD Cohort 3: TAK-915 200 mg; SRD Cohorts 1-3: Placebo

Midazolam DRUG

Midazolam oral solution

Also known as: Versed

BA/FE Cohort 9 Group 1: B,C,A

Placebo DRUG

Placebo-matching TAK-915 suspension

BA/FE Cohort 10 Group 1: C,A,B

TAK-915 tablet DRUG

TAK-915 tablet

ESSD Cohort 11: TAK-915 50 mg

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 healthy man or woman, aged 18 to 55 years, inclusive at the time of informed consent and first study medication dose for all cohorts will be included. Note that Cohort 12 will enroll healthy, elderly men and women, aged 65 to 75 years, inclusive.
• Weighs at least 50 kg and has a body mass index (BMI) from 18.0 to 35.0 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 with no childbearing potential, defined as the participant has been surgically sterilized (hysterectomy, bilateral oophorectomy or tubal ligation) or who are postmenopausal (defined as continuous amenorrhea of at least 2 y ears and follicle stimulating hormone (FSH) \>40 IU/L).

You may not qualify if:

• Has received any investigational compound within 30 days prior to the first dose of study medication.
• Has received TAK-915 in a previous clinical study or as a therapeutic agent.
• Is an immediate family member, study site employee, or is 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, gastrointestinal, urologic, immunologic, endocrine disease, or psychiatric disorder, 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 TAK-915 and/or midazolam.
• If female, the participant is of childbearing potential (eg. premenopausal, not sterilized).
• 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 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.
• Has taken any excluded medication, supplements, or food products during the time periods listed in the Excluded Medications and Dietary Products table.
• Is pregnant or lactating or intending to become pregnant before, during, or within 12 weeks after participating in this study ; 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 after the last dose of study medication.
• 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-915, 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 mental retardation or medical condition that can cause cognitive impairment.
• Has current or recent (within 6 months) gastrointestinal 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, except basal cell carcinoma which has been in remission for at least 5 years prior to Check-in (Day -1).

Sponsors & Collaborators

• Takeda: lead

Study Sites (1)

Unknown Facility

Austin, Texas, United States

Location

MeSH Terms

Interventions

Midazolam; TAK-915

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

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: May 29, 2015
• First Posted: June 3, 2015
• Study Start: May 12, 2015
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2016
• Last Updated: February 15, 2019
• Results First Posted: February 15, 2019

Record last verified: 2018-10

Locations

US (1)