Clinical trial NCT02175784: A Study to Assess the Efficacy and Safety of Ipragliflozin in Combination With Insulin in Subjects With Type 2 Diabetes Mellitus
Official title: Postmarketing Clinical Study of Ipragliflozin - Double-blind, Parallel-group Study in Combination With Insulin in Patients With Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetes Mellitus
Keywords: Blood glucose
insulin
ipragliflozin
SGLT2 inhibitor
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2014-06-26
Enrollment: 262
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the efficacy (superiority to placebo) of ipragliflozin based on the changes in HbA1C, as well as its safety, in patients with type 2 diabetes mellitus in combination with an insulin preparation once daily for 16 weeks. The long-term (52 weeks) safety and the persistence of the efficacy will also be evaluated.

Detailed description: This study consists of two parts. First part is a placebo-controlled multicenter, double-blind, parallel group study, in which subjects will receive ipragliflozin or placebo once daily in combination with an insulin preparation for 16 weeks. Second part is a multicenter, open-label period (36 weeks) with no placebo group. The dose of ipragliflozin can be doubled in combination with an insulin preparation during the second part.

Eligibility criteria: Inclusion Criteria:

* Subject has been diagnosed with type 2 diabetes mellitus for at least 12 weeks (84 days) at signing of informed consent.
* Subject takes constant dosage and administration of insulin preparation for more than 6 weeks (42 days)
* Subject has an HbA1C value between 7.5 and 10.0% at Visit 2 and the difference of HbA1C value within ± 1.0% between Visit 1 and Visit 2
* Subject has a body mass index (BMI) 20.0 - 45.0 kg/m2

Exclusion Criteria:

* Subject has type 1 diabetes mellitus
* Subject has proliferative diabetic retinopathy
* Subject has a history of clinically significant renal disease such as renovascular occlusive disease, nephrectomy and/or renal transplant
* Subject has a history of recurrent urinary tract infection (more than three times within before 24 weeks of obtaining informed consent)
* Subject has a symptomatic urinary tract infection or symptomatic genital infection
* Subject has chronic disease which requires the continuous use of adrenocortical steroids and immunosuppressant (oral medication, injection, or inhalation)
* Subject has a history of cerebral vascular attack, unstable angina, myocardial infarction, vascular intervention, and heart disease (NYHA Class III-IV) within 1 year (52 weeks) prior to Visit 1
* Subject has unstable psychiatric disorder
* Female subject who is currently pregnant or lactating, or who is possibly pregnant
* Male and pre-menopausal female subject who cannot use an appropriate contraception during the study
* Subject has severe infection, perioperative, or serious trauma
* Subject has drug addiction or alcohol abuse
* Subject has a history of malignant tumors (except for those who have not received treatment for malignant tumors for at least 5 years before informed consent acquisition and was not considered to have recurrence)
* Subject has a history of an allergy with ipragliflozin and/or similar drugs (study drugs possessing SGLT 2 inhibitory action)
* Subject has participated in another clinical study, post marketing study, or medical equipment study within 12 weeks (84 days) before providing written informed consent, or who is currently participating in any of those studies
* Subject is unable, unwilling to adhere to compliances such as hospital visits and dose instruction specified in this study

Primary outcomes:
measure: Change in HbA1C from baseline
timeFrame: Baseline and Week 16
Secondary outcomes:
measure: Fasting plasma glucose
timeFrame: Baseline, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
measure: Leptin concentration
timeFrame: Baseline, Week 2, 4, 8, 12, 16, 24, 36, 52
measure: Fructosamine concentration
timeFrame: Baseline, Week 2, 4, 8, 12, 16, 24, 36, 52
measure: Adiponectin concentration
timeFrame: Baseline, Week 2, 4, 8, 12, 16, 24, 36, 52
measure: Body weight
timeFrame: Baseline, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
measure: Waist circumference
timeFrame: Baseline, Week 16, 24, 52
measure: Blood glucose values of self monitoring
timeFrame: Baseline, Week 8, 16, 24, 52
measure: Safety assessed by the adverse events, vital signs. and laboratory tests
timeFrame: Up to 52 Weeks
Other outcomes:
Locations:
city: Chubu
country: Japan
city: Chugoku
country: Japan
city: Hokkaido
country: Japan
city: Kansai
country: Japan
city: Kanto
country: Japan
city: Kyushu
country: Japan
city: Shikoku
country: Japan
city: Touhoku
country: Japan
Study officials:
affiliation: Astellas Pharma Inc
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Kashiwagi A, Shestakova MV, Ito Y, Noguchi M, Wilpshaar W, Yoshida S, Wilding JPH. Safety of Ipragliflozin in Patients with Type 2 Diabetes Mellitus: Pooled Analysis of Phase II/III/IV Clinical Trials. Diabetes Ther. 2019 Dec;10(6):2201-2217. doi: 10.1007/s13300-019-00699-8. Epub 2019 Oct 12.
citation: Ishihara H, Yamaguchi S, Nakao I, Asahina S, Sakatani T. Efficacy and safety of ipragliflozin as add-on therapy to insulin in Japanese patients with type 2 diabetes mellitus (IOLITE): a 36-week, open-label extension of a 16-week, randomized, placebo-controlled, double-blind study. Diabetol Int. 2018 Jul 16;10(1):37-50. doi: 10.1007/s13340-018-0359-x. eCollection 2019 Jan.