The PK and PD of dapagliflozin therapy in combination with insulin in Japanese subjects with T1DM

Study identifier:D1695C00001sub

ClinicalTrials.gov identifier:NCT02582840

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A clinical pharmacology and long term study to evaluate the safety, efficacy, pharmacokinetics and pharmacodynamics of dapagliflozin therapy in combination with insulin in Japanese subjects with type 1 diabetes who have inadequate glycemic control

Medical condition

Type 1 Diabetes Mellitus

Phase

Phase 1

Healthy volunteers

Study drug

Dapagliflozin 5mg, Dapagliflozin 10mg, Placebo tablet

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 65 Years

Date

Study Start Date: 01 Oct 2015

Primary Completion Date: 01 Jun 2016

Study Completion Date: 01 Jun 2016

Study design

Allocation: Randomized
Endpoint Classification: Pharmacokinetics/dynamics
Intervention Model: Parallel Assignment
Masking: Single Blind
Primary Purpose: Basic Science

Verification:

Verified 01 Aug 2018 by AstraZeneca

Collaborators

Inclusion and exclusion 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 < 0.7 ng/mL Subject re-enrolment: This study does not permit the re-enrolment of a subject who has discontinued the study as a screen failure
-Insulin use for at least 12 months prior to the enrolment per subject report or medical records and Method of insulin administration (MDI) must have been unchanged for at least 3 months prior to the enrolment per subject report or medical records. Subjects must be taking a total daily insulin dose of ≥ 0.3 U/kg/day for at least 3 months prior to the enrolment. CSII users are excluded. MDI insulin administration subject must be on ≥ 3x injections per day.
- Gender and reproductive Status Japanese men and women.
- HbA1c eligibility criteria include: Screening Visit: Central laboratory HbA1c ≥ 7.0 % and ≤ 10.0 % (One repeat HbA1c test for subjects in screening if their initial test result was an HbA1c ± 0.2% of the cut off values)
- BMI ≥ 20.0 kg/m², ≤ 35.0 kg/m² at visit 1
- Ages 18 to 65 years, inclusive - ≥ 18 years old and < 20 years old must have assent forms signed and dated by their parents or guardians

Exclusion Criteria

-Target Disease Exceptions History of T2DM In cases where the subject has a history of T2DM and has a documented history of being auto-antibody positive for GAD65, tyrosine phosphatase IA-2/IA-2β, or Zinc Transporter 8 (ZnT8), or fasting c-peptide value below the lower limit of detection performed by local or central laborator, the subject will be eligible for screening
-Maturity onset diabetes of young (MODY), Pancreatic surgery, chronic pancreatitis, or other pancreatic disorders that could result in decreased β-cell capacity (eg, pancreatogenous diabetes)
-Any antihyperglycemic agent use, other than thiazolidinediones, or insulin, within 1 month prior to the screening visit. Use of thiazolidinediones within 6 months prior to the screening visit.
-History of DKA requiring medical intervention (eg, emergency room visit and/or hospitalization) within 1 month prior to the enrolment
-History of hospital admission for glycemic control (either hyperglycemia or hypoglycemia) within 1 month prior to the enrolment
-Malignancy within 5 years of the enrolment (with the exception of treated basal cell or treated squamous cell carcinoma)
-History of bladder cancer
-History of radiation therapy to the lower abdomen or pelvis at any time Unstable pre-proliferative and proliferative retinopathy (untreated or under treatment).
- Physical and Laboratory Test Findings
Aspartate aminotransferase (AST) > 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

No locations available

Arms	Assigned Interventions
Experimental: dapagliflozin 5mg dapagliflozin tablet 5mg	Drug: Dapagliflozin 5mg Dapagliflozin, a blood glucose lowering drug. Oral dose
Experimental: dapagliflozin 10mg dapagliflozin tablet 10mg	Drug: Dapagliflozin 10mg Dapagliflozin, a blood glucose lowering drug. Oral dose
Placebo Comparator: Placebo dapagliflozin tablet 5mg placebo or 10 mg placebo	Drug: Placebo tablet Placebo tablet. Oral dose

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]