Phase 1
Completed N=42
The PK and PD of Dapagliflozin Therapy in Combination With Insulin in Japanese Subjects With T1DM
Source: ClinicalTrials.gov NCT02582840 ↗Enrolled (actual)
42
Serious AEs
0.0%
Results posted
Jan 2019
Primary outcomePrimary: Dapagliflozin Maximum Observed Plasma Concentration (Cmax) of 7 Days Repeated Doses of Dapagliflozin - Pharmacokinetic (PK) Set — 69.31; 162.09 ng/mL
Summary
This randomized, single-blind, 3 arm, parallel group, placebo controlled PK/PD study will enrol 30 Japanese male and female patients with T1DM and age 18 to 65 years, with inadequate glycemic control on insulin defined as HbA1c ≥ 7.0% and ≤ 10.0% at screening visit. lacebo-controlled design. Patients will be randomized in a 1:1:1 ratio into one of the 3 single-blinded treatment arms; dapagliflozin 5 mg, dapagliflozin 10 mg or placebo. CSII user are excluded.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Dapagliflozin Maximum Observed Plasma Concentration (Cmax) of 7 Days Repeated Doses of Dapagliflozin - Pharmacokinetic (PK) Set |
69.31; 162.09 | — |
| PRIMARY Dapagliflozin Minimum Observed Plasma Concentration (Cmin) of 7 Days Repeated Doses of Dapagliflozin - Pharmacokinetic (PK) Set |
3.40; 5.71 | — |
| PRIMARY Dapagliflozin Time of Maximum Observed Plasma Concentration (Tmax) of 7 Days Repeated Doses of Dapagliflozin - Pharmacokinetic (PK) Set |
2.00; 2.00 | — |
| PRIMARY Dapagliflozin Area Under the Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration AUC(0-T) of 7 Days Repeated Doses of Dapagliflozin - Pharmacokinetic (PK) Set |
322.72; 670.01 | — |
| PRIMARY Dapagliflozin 3-O-Glucuronide Maximum Observed Plasma Concentration (Cmax) of 7 Days Repeated Doses of Dapagliflozin - Pharmacokinetic (PK) Set |
61.88; 136.62 | — |
| PRIMARY Dapagliflozin 3-O-Glucuronide Minimum Observed Plasma Concentration (Cmin) of 7 Days Repeated Doses of Dapagliflozin - Pharmacokinetic (PK) Set |
3.89; 6.25 | — |
| PRIMARY Dapagliflozin 3-O-Glucuronide Time of Maximum Observed Plasma Concentration (Tmax) of 7 Days Repeated Doses of Dapagliflozin - Pharmacokinetic (PK) Set |
2.00; 2.00 | — |
| PRIMARY Dapagliflozin 3-O-Glucuronide Area Under the Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration AUC(0-T) of 7 Days Repeated Doses of Dapagliflozin - Pharmacokinetic (PK) Set |
345.87; 675.50 | — |
| PRIMARY Dapagliflozin Ratio of Metabolite to Parent AUC of 7 Days Repeated Doses of Dapagliflozin - Pharmacokinetic (PK) Set |
0.75; 0.70 | — |
| PRIMARY 24-hour Urinary Glucose (g/24h) Mean Change From Baseline on Day 7 - Pharmacodynamic (PD) Set |
-6.16; 96.55; 101.28 | — |
| SECONDARY Total Daily Insulin (IU) Percent Change From Baseline to Day 7 - Pharmacodynamic (PD) Set |
-4.97; -36.86; -39.13 | — |
| SECONDARY Daily Basal Insulin (IU) Percent Change From Baseline to Day 7 - Pharmacodynamic (PD) Set |
-16.75; -36.74; -39.63 | — |
| SECONDARY Daily Bolus Insulin (IU) Percent Change From Baseline to Day 7 - Pharmacodynamic (PD) Set |
4.56; -36.06; -39.89 | — |
| SECONDARY Fasting Plasma Glucose (FPG) (mg/dL) Change From Baseline to Day 7 - Pharmacodynamic (PD) Set |
11.0; -10.4; -13.1 | — |
| SECONDARY Seated Systolic Blood Pressure (mmHG) Change From Baseline to Day 7 - Pharmacodynamic (PD) Set |
-3.1; -2.1; 1.5 | — |
Eligibility Criteria
Inclusion Criteria
- Signed Written Informed Consent Subjects or their legally responsible representatives must be willing and able to give signed and dated written informed consent.
- Target Population Diagnosis of T1DM. In addition, the following criteria also needs to be met; Central laboratory test of C-peptide 3x upper limit of normal (ULN) Alanine aminotransferase (ALT) > 3x ULN Serum total bilirubin (TB) > 2.0 mg/dL (34.2 μmol/L).
- Estimated GFR (eGFR) by the Japanese Society of Nephrology formula ≤ 60 mL/min/1.73m2. Hemoglobin ≤ 11.0 g/dL (110 g/L) for men; hemoglobin ≤ 10.0 g/dL (100 g/L) for women.
- Positive for hepatitis B surface antigen or anti-hepatitis C virus antibody
- Abnormal Free T4
Data sourced from ClinicalTrials.gov (NCT02582840). 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.