TAK-648 Multiple-Rising Dose Study in Healthy Japanese Participants and Non-Japanese Participants With Type 2 Diabetes Mellitus

NCT02430870 | Completed Phase 1 Results

• 2 other identifiers: TAK-648-1002U1111-1165-3437
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 2

Brief Summary

This is a phase 1, randomized, double-blind, placebo-controlled, 2-center, multiple-dose study in healthy participants and participants with type 2 diabetes mellitus (T2DM). This study will evaluate the safety, tolerability and pharmacokinetics (PK) of TAK-648 when administered as multiple oral doses of TAK-648 solution at escalating dose levels in healthy participants of Japanese decent and participants with T2DM.

Conditions

Type 2 Diabetes Mellitus

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (8)

• Percentage of Participants Who Have at Least 1 Treatment-Emergent Adverse Event (TEAE) for Part 1

  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. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.

  Up to Day 34

• Percentage of Participants Who Have at Least 1 Treatment-Emergent Adverse Event (TEAE) for Part 2

  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. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.

  Up to Day 26

• Percentage of Participants With Markedly Abnormal Laboratory Values at Least Once Post-dose During Dosing for Part 1

  Up to Day 20

• Percentage of Participants With Markedly Abnormal Laboratory Values at Least Once Post-dose During Dosing for Part 2

  Up to Day 13

• Percentage of Participants With Markedly Abnormal Vital Sign Values at Least Once Post-dose During Dosing for Part 1

  Vital signs included body temperature (oral), sitting blood pressure (after 5 minutes resting), respiration rate and pulse (bpm).

  Up to Day 20

• Percentage of Participants With Markedly Abnormal Vital Sign Values at Least Once Post-dose During Dosing for Part 2

  Vital signs included body temperature (oral), sitting blood pressure (after 5 minutes resting), respiration rate and pulse (bpm),

  Up to Day 13

• Percentage of Participants Who Have Severe Hypoglycemia at Least Once Post-dose During Dosing For Part 1

  Severe hypoglycemia was defined as an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions.

  Up to Day 20

• Percentage of Participants Who Have Severe Hypoglycemia at Least Once Post-dose During Dosing For Part 2

  Severe hypoglycemia was defined as an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions.

  Up to Day 13

Secondary Outcomes (10)

• Cmax: Maximum Plasma Concentration for TAK-648 for Part 1

  Days 1 and 17 pre-dose and multiple time-points post-dose (Up to 72 hours)

• Cmax: Maximum Plasma Concentration for TAK-648 for Part 2

  Days 1 and 10 pre-dose and multiple time-points post-dose (Up to 72 hours)

• Tmax: Time to Reach Maximum Plasma Concentration (Tmax) for TAK-648 for Part 1

  Days 1 and 17 pre-dose and multiple time-points post-dose (Up to 72 hours)

• Tmax: Time to Reach Maximum Plasma Concentration (Tmax) for TAK-648 for Part 2

  Days 1 and 10 pre-dose and multiple time-points post-dose (Up to 72 hours)

• AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-648 for Part 1

  Days 1 and 17 pre-dose and multiple time-points post-dose (Up to 72 hours)

Study Arms (8)

Part 1 Cohort 1: TAK-648 0.35 mg

EXPERIMENTAL

Participants with T2DM on a stable dose of metformin in study Part 1, Cohort 1 received TAK-648 0.35 mg, solution, orally, single dose on Day 1, no drug administration on Days 2 to 3, followed by once daily (QD) doses starting on Day 4 and continuing through Day 17 (14 days).

Drug: TAK-648

Part 1 Cohort 2: TAK-648 0.80 mg

EXPERIMENTAL

Participants with T2DM on a stable dose of metformin in study Part 1, Cohort 2 received TAK-648 0.80 mg, solution, orally, single dose on Day 1, no drug administration on Days 2 to 3, followed by once daily (QD) doses starting on Day 4 and continuing through Day 17 (14 days).

Drug: TAK-648

Part 1: Placebo Cohort 1-2

PLACEBO COMPARATOR

Participants with T2DM on a stable dose of metformin in study Part 1 received placebo-matching TAK-648, solution, orally, single dose on Day 1, no drug administration on Days 2 to 3, followed by once daily (QD) doses starting on Day 4 and continuing through Day 17 (14 days).

Drug: Placebo

Part 2 Cohort 1: TAK-648 0.05 mg

EXPERIMENTAL

Healthy participants of Japanese descent in study Part 2, Cohort 1 received TAK-648 0.05 mg, solution , orally, single dose on Day 1, no drug administration on Days 2 to 3, followed by multiple QD doses starting on Day 4 and continuing through Day 10 (7 days).

Drug: TAK-648

Part 2 Cohort 2: TAK-648 0.15 mg

EXPERIMENTAL

Healthy participants of Japanese descent in study Part 2, Cohort 2 received TAK-648 0.15 mg, solution, orally, single dose on Day 1, no drug administration on Days 2 to 3, followed by multiple QD doses starting on Day 4 and continuing through Day 10 (7 days).

Drug: TAK-648

Part 2 Cohort 3: TAK-648 0.35 mg

EXPERIMENTAL

Healthy participants of Japanese descent in study Part 2, Cohort 3 received TAK-648 0.35 mg, solution, orally, single dose on Day 1, no drug administration on Days 2 to 3, followed by multiple QD doses starting on Day 4 and continuing through Day 10 (7 days).

Drug: TAK-648

Part 2 Cohort 4: TAK-648 0.80 mg

EXPERIMENTAL

Healthy participants of Japanese descent in study Part 2, Cohort 4 received TAK-648 0.80 mg, solution, orally, single dose on Day 1, no drug administration on Days 2 to 3, followed by multiple QD doses starting on Day 4 and continuing through Day 10 (7 days).

Drug: TAK-648

Part 2: Placebo Cohort 1-4

PLACEBO COMPARATOR

Healthy participants of Japanese descent in study Part 2, received TAK-648 placebo-matching solution, orally, single dose on Day 1, no drug administration on Days 2 to 3, followed by multiple QD doses starting on Day 4 and continuing through Day 10 (7 days).

Drug: Placebo

Interventions

TAK-648 DRUG

TAK-648 solution

Part 1 Cohort 1: TAK-648 0.35 mg; Part 1 Cohort 2: TAK-648 0.80 mg; Part 2 Cohort 1: TAK-648 0.05 mg; Part 2 Cohort 2: TAK-648 0.15 mg; Part 2 Cohort 3: TAK-648 0.35 mg; Part 2 Cohort 4: TAK-648 0.80 mg

Placebo DRUG

TAK-648 placebo-matching solution

Part 1: Placebo Cohort 1-2; Part 2: Placebo Cohort 1-4

Eligibility Criteria

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

You may qualify if:

• Part 1:
• Is an adult male or female and has a historical diagnosis of type 2 diabetes mellitus (T2DM) disease.
• Is aged 18 to 65 years, inclusive, at the time of informed consent and first study medication dose.
• Weighs at least 55 kg and has a body mass index (BMI) ≥23.0 kg/m\^2 and ≤35.0 kg/m\^2 at Screening.
• Has a systolic blood pressure \>90 and ≤150 mm Hg and a diastolic blood pressure of \>60 and ≤90 mm Hg at Screening and at Check-in (Day -2). If out of range, may be repeated once for eligibility determination within a maximum of5 minutes.
• Has a calculated creatinine clearance \>60 mL/min at Screening and Check-in (Day -2).
• Has been treated for inadequate glycemic control with a stable dose of metformin for the least 8 weeks prior to Screening.
• Has a glycosylated hemoglobin (HbA1c) level between 6.5% and 10.0%, inclusive at Check-in (Day -2).
• Has a fasting C-peptide concentration ≥0.8 ng/mL at Screening.
• Has no medical history of type 1 diabetes mellitus (T1DM), hypoglycemia unawareness, diabetic ketoacidosis or hyperosmolar coma.
• Part 2:
• Is a healthy adult male or female of Japanese descent (born to Japanese parents and grandparents) and have lived outside of Japan for less than 5 years, inclusive.
• Is aged 20 to 55 years, inclusive, at the time of informed consent and first study medication dose.
• Weighs at least 45 kg and has a BMI from 17.0 to 25.0 kg/m\^2, inclusive at Screening.
• Has a systolic blood pressure \>90 and ≤150 mm Hg and a diastolic blood pressure of \>60 and ≤90 mm Hg at Screening and at Check-in (Day -2). If out of range, may be repeated once for eligibility determination within a maximum of 5 minutes.

You may not qualify if:

• Part 1:
• Has Screening or Check-in (Day -2) laboratory values of serum creatinine ≥1.5 mg/dL for males or ≥1.4 mg/dL \[females\] or abnormal creatinine clearance.
• Has a history of T1DM, hypoglycemia unawareness, diabetic ketoacidosis, or hyperosmolar coma.
• Has a history of any clinically significant retinopathy, which is defined as more than moderate nonproliferative diabetic retinopathy or any stage of proliferative diabetic retinopathy or any history of laser-treated retinopathy.
• Has received any antihyperglycemic medication with the exception of metformin within the previous 12 weeks of Check-in (Day -2) or the subject has changed the dose of metformin within the previous 8 weeks of Screening.
• Is expecting to receive, receiving or has received systemic glucocorticoid therapy for a duration longer than 5 days within the previous 12 weeks of Check-in (Day -2).
• Parts 1 and 2:
• Has received any investigational compound within 30 days prior to the first dose of study medication.
• Has received TAK-648 in a previous clinical study or as a therapeutic agent.
• Has any significant medical histories or currently uncontrolled clinical conditions, which may not be safe for participants to participate in the study, may impact the ability of the participant to participate in the study, or may potentially confound the study results. The concerned significant medical histories and uncontrolled clinical conditions include (may not be limited to) cardiovascular (such as ischemic heart disease, heart failure, cardiomyopathy, clinically significant arrhythmia, uncontrolled or unstable blood pressure), central nervous system, hepatic or hematopoietic disease(s), renal dysfunction, metabolic or endocrine dysfunction, pulmonary diseases including serious allergy and asthma hypoxemia, seizures, or allergic skin rash.
• Has a history of significant GI disorders manifested with persistent, chronic or intermittent nausea, vomiting or diarrhea, or has a current or recent (within 6 months) GI disease that would influence the absorption of drugs (eg, a history or malabsorption, severe esophageal reflux, peptic ulcer disease or erosive esophagitis with frequent \[more than once per week\] occurrence of heartburn).
• Has diagnosis of major depression, bipolar disorder or anxiety disorders, or has a risk of anxiety, depression, or insomnia according to the investigator's clinical judgment per HAM-D17 at Screening or has received any medication to treat any psychological disorders within 1 year.
• Has a risk of suicide according to the investigator's clinical judgment per C-SSRS at Screening or has made a suicide attempt in the past 6 months prior to Screening.
• Has a known hypersensitivity to any component of the formulation ofTAK-648, or to a PDE4 inhibitor (eg, roflumilast) or Listerine strips.
• Has a positive urine drug result for drugs of abuse at Screening or Check-in (Day -2).

Sponsors & Collaborators

• Takeda: lead

Study Sites (2)

Unknown Facility

Anaheim, California, United States

Location

Unknown Facility

Chula Vista, California, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Medical Director Clinical Science
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director

  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: April 24, 2015
• First Posted: April 30, 2015
• Study Start: April 1, 2015
• Primary Completion: September 1, 2015
• Study Completion: November 1, 2015
• Last Updated: August 31, 2016
• Results First Posted: August 31, 2016

Record last verified: 2016-07

Locations

US (2)