TAK-648 in Healthy Japanese Participants and Non-Japanese Participants With Type 2 Diabetes Mellitus

Type 2 Diabetes Mellitus Clinical Trial

Official title:

A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Safety, Tolerability, and Pharmacokinetic Study of Escalating Multiple Oral TAK-648 Doses in Healthy Japanese Subjects and Subjects With Type 2 Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02430870
• Other study ID #: TAK-648-1002
• Status: Completed
• Phase: Phase 1
• First received: April 24, 2015
• Last updated: December 7, 2015
• Start date: April 2015
• Est. completion date: October 2015

Study information

• Verified date: December 2015
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

Description:

The drug being evaluated in this study is TAK-648 for the treatment of T2DM.

This study will consist of 2 parts: (1) multiple ascending doses in participants with T2DM, (2) multiple ascending doses in healthy participants of Japanese descent.

Part 1 of this study will consist of 2 multiple dose treatment cohorts (Cohorts 1-2 designated as P1C1and P1C2) dosed sequentially in escalating order. The projected doses of TAK-648 for Part 1 are 0.15 and 0.35 mg of TAK-648, but may be adjusted higher or lower, and additional cohorts may be added, based on available safety and pharmacokinetic (PK) data. All cohorts in Part 1 will consist of 8 (2 placebo) T2DM participants.

Part 2 of this study will consist of 3 multiple dose treatment cohorts (Cohorts 1-3 designated as P2C1, P2C2 and P2C3) in healthy participants of Japanese descent dosed sequentially in escalating order. The projected doses of TAK-648 chosen for Part 2 are 0.05, 0.15 and 0.35 mg of TAK-648, but may be adjusted higher or lower based on available safety and PK data. All cohorts in Part 2 will consist of 8 (2 placebo) healthy participants of Japanese descent.

Additional cohorts may be recruited and studied as necessary to better evaluate safety, tolerability, PK, and/or PD parameters.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: October 2015
• Est. primary completion date: September 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 20 Years to 64 Years

Eligibility

Inclusion Criteria:

Part 1:

• has a historical diagnosis of T2DM disease, on diet and exercise or on metformin

• weighs at least 55 kg and has a body mass index (BMI) from 25.0 to 30.0 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)

• has a calculated creatinine clearance >60 mL/min at Screening and Check-in (Day -2)

• hemoglobin A1c (HbA1c) level between 7.0% and 10.0%, inclusive

Part 2:

• Health participants of Japanese origin

Exclusion Criteria:

Part 1 and Part 2:

• has received any investigational compound within 30 days prior to the first dose of study medication

• history of significant gastrointestinal (GI) disorders Part 1, has diagnosis of major depression and risk of suicide, Part 1, 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

• intends to donate sperm during the course of this study or for 12 weeks thereafter

• has a history of cancer, 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 (HBsAg), antibody to hepatitis C virus (anti-HCV), at Screening or a known history of human immunodeficiency virus infection

• 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 -2). Cotinine test is positive at Screening or Check-in (Day -2)

• history of T1DM, hypoglycemia unawareness, diabetic ketoacidosis, or hyperosmolar coma

• has received any antihyperglycemic medication with the exception of metformin within the previous 12 weeks of Check-in (Day -2)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• TAK-648
TAK-648 administered orally once daily for 15 days.
• Placebo
Matching placebo to TAK-648 administered orally once daily for 15 or 8 days for part 1 and part 2 respectively.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of participants who have at least 1 treatment-emergent adverse event (TEAE) for Part 1.		Up to Day 34	Yes
Primary	Percentage of participants who have at least 1 treatment-emergent adverse event (TEAE) for Part 2.		Up to 26 days	Yes
Primary	Percentage of participants with markedly abnormal criteria for safety laboratory tests at least once postdose during dosing for Part 1	Laboratory evaluations of participants were collected to determine if they met the Takeda Development Center (TDC) markedly abnormal criteria for safety laboratory tests at least once postdose during the dosing interval.	Up to Day 20	Yes
Primary	Percentage of participants with markedly abnormal criteria for safety laboratory tests at least once postdose during dosing for Part 2	Laboratory evaluations of participants were collected to determine if they met the Takeda Development Center (TDC) markedly abnormal criteria for safety laboratory tests at least once postdose during the dosing interval.	Up to Day 13	Yes
Primary	Percentage of partcipants with markedly abnormal criteria for vital signs for Part 1		Up to Day 20	Yes
Primary	Percentage of partcipants with markedly abnormal criteria for vital signs for Part 2		Up to Day 13	Yes
Primary	Percentage of subjects who have severe hypoglycemia at least once postdose during dosing for Part 1		Up to Day 34	Yes
Primary	Percentage of subjects who have severe hypoglycemia at least once postdose during dosing for Part 2		Up to Day 26	Yes
Secondary	Maximum plasma concentration (Cmax) of TAK-648 for Part 1	Participant blood samples were collected to determine the maximum plasma concentration of TAK-648 following dosing.	Up to Day 20	No
Secondary	Maximum plasma concentration (Cmax) of TAK-648 for Part 2	Participant blood samples were collected to determine the maximum plasma concentration of TAK-648 following dosing.	Up to Day 13	No
Secondary	Time to maximum plasma concentration (Tmax) of TAK-648 for Part 1	Participant blood samples were collected to determine the time to the maximum plasma concentration of TAK-648 following dosing	Up to Day 20	No
Secondary	Time to maximum plasma concentration (Tmax) of TAK-648 for Part 2	Participant blood samples were collected to determine the time to the maximum plasma concentration of TAK-648 following dosing.	Up to Day 13	No
Secondary	Area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration (AUCt) for Part 1	Participant blood samples were collected to determine the area under the curve from time 0 to the time to the last quantifiable concentration of TAK-648 following dosing.	Up to Day 20	No
Secondary	Area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration (AUCt) for Part 2	Participant blood samples were collected to determine the area under the curve from time 0 to the time to the last quantifiable concentration of TAK-648 following dosing.	Up to Day 13	No
Secondary	AUC from time 0 to infinity (AUC8) of TAK-648 for Part 1	Participant blood samples were collected following a single dose of TAK-648 to determine the AUC8.	Up to Day 20	No
Secondary	AUC from time 0 to infinity (AUC8) of TAK-648 for Part 2	Participant blood samples were collected following a single dose of TAK-648 to determine the AUC8.	Up to Day 13	No
Secondary	Area under the plasma concentration-time curve during a dosing interval (AUC ?) for Part 1	Participant blood samples were collected to determine the area under the concentration-time curve during a dosing interval where tau (?) is the length of the dosing interval.	Up to Day 20	No
Secondary	Area under the plasma concentration-time curve during a dosing interval (AUC ?) for Part 2	Participant blood samples were collected to determine the area under the concentration-time curve during a dosing interval where tau (?) is the length of the dosing interval.	Up to Day 13	No