Phase 1
Completed N=16
TAK-648 Multiple-Rising Dose Study in Healthy Japanese Participants and Non-Japanese Participants With Type 2 Diabetes Mellitus
Source: ClinicalTrials.gov NCT02430870 ↗Enrolled (actual)
16
Serious AEs
0.0%
Results posted
Aug 2016
Primary outcomePrimary: Percentage of Participants Who Have at Least 1 Treatment-Emergent Adverse Event (TEAE) for Part 1 — 83.3; 33.3; 100.0 percentage of participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants Who Have at Least 1 Treatment-Emergent Adverse Event (TEAE) for Part 1 |
83.3; 33.3; 100.0 | — |
| PRIMARY Percentage of Participants Who Have at Least 1 Treatment-Emergent Adverse Event (TEAE) for Part 2 |
100.0; 33.3; 66.7; 83.3; 37.5 | — |
| PRIMARY Percentage of Participants With Markedly Abnormal Laboratory Values at Least Once Post-dose During Dosing for Part 1 |
0; 0; 0 | — |
| PRIMARY Percentage of Participants With Markedly Abnormal Laboratory Values at Least Once Post-dose During Dosing for Part 2 |
0; 0; 0; 0; 0 | — |
| PRIMARY Percentage of Participants With Markedly Abnormal Vital Sign Values at Least Once Post-dose During Dosing for Part 1 |
0; 16.7; 50.0; 16.7; 0; 0 | — |
| PRIMARY Percentage of Participants With Markedly Abnormal Vital Sign Values at Least Once Post-dose During Dosing for Part 2 |
50.0; 50.0; 33.3; 33.3; 37.5; 0 | — |
| PRIMARY Percentage of Participants Who Have Severe Hypoglycemia at Least Once Post-dose During Dosing For Part 1 |
0; 0; 0 | — |
| PRIMARY Percentage of Participants Who Have Severe Hypoglycemia at Least Once Post-dose During Dosing For Part 2 |
0; 0; 0; 0; 0 | — |
| SECONDARY Cmax: Maximum Plasma Concentration for TAK-648 for Part 1 |
6.342; 16.150; 7.950; 16.283 | — |
| SECONDARY Cmax: Maximum Plasma Concentration for TAK-648 for Part 2 |
0.764; 1.955; 5.925; 10.080; 0.670; 2.355 | — |
| SECONDARY Tmax: Time to Reach Maximum Plasma Concentration (Tmax) for TAK-648 for Part 1 |
0.500; 1.000; 0.500; 0.710 | — |
| SECONDARY Tmax: Time to Reach Maximum Plasma Concentration (Tmax) for TAK-648 for Part 2 |
1.000; 1.000; 1.000; 1.000; 1.500; 0.750 | — |
| SECONDARY 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 |
31.676; 88.168; 43.908; 107.492 | — |
| SECONDARY AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-648 for Part 2 |
5.018; 14.861; 38.878; 63.376; 5.355; 19.274 | — |
| SECONDARY AUC∞: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-648 for Part 1 |
31.973; 89.043; 46.827; 110.882 | — |
| SECONDARY AUC∞: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-648 for Part 2 |
5.147; 15.078; 39.160; 64.694; 5.538; 19.922 | — |
| SECONDARY AUCtau: Area Under the Plasma Concentration-time Curve From Time 0 Over the Dosing Interval for TAK-648 for Part 1 |
30.209; 82.148; 39.283; 95.028 | — |
| SECONDARY AUCtau: Area Under the Plasma Concentration-time Curve From Time 0 Over the Dosing Interval for TAK-648 for Part 2 |
4.833; 13.902; 36.570; 59.507; 5.036; 17.215 | — |
Eligibility Criteria
Inclusion Criteria
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.
- Has a calculated creatinine clearance >60 mL/min at Screening and Check-in (Day -2).
Exclusion Criteria
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
Data sourced from ClinicalTrials.gov (NCT02430870). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.