Clinical trial NCT02847091: Study of Ipragliflozin in Patients With Type 2 Diabetes Mellitus Receiving Insulin Therapy
Official title: Post-marketing Clinical Study of Ipragliflozin; Multicenter, Open-label Study to Assess the Efficacy of Ipragliflozin Add-on in Reducing Insulin Dose in Patients With Type 2 Diabetes Mellitus Receiving Insulin Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetes Mellitus
Keywords: Ipragliflozin
SGLT2 inhibitor
Type 2 diabetes mellitus
ASP1941
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2016-07-28
Enrollment: 103
Sex: ALL
Minimum age (years): 20
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The objective of this study is to assess the reduction in insulin dose from baseline at Week 24 while keeping the blood glucose levels controlled (maintaining HbA1c values) when ipragliflozin is administered once daily for 24 weeks in patients with type 2 diabetes mellitus receiving insulin therapy.


Eligibility criteria: Inclusion Criteria:

* The subject has been receiving insulin therapy for the treatment of diabetes mellitus.
* The subject has type 2 diabetes mellitus and has been receiving insulin monotherapy or insulin therapy in combination with one or two oral hypoglycemic agents.
* The subject has not modified diet or exercise therapies or dosage regimen of oral hypoglycemic agents, or has not switched to another pharmacotherapy for 12 weeks before Visit 1.
* The subject has an HbA1c value between 6.5% and \<8.0%.
* The subject has a body mass index (BMI) of \>23.0 kg/m2.
* If the subject is a female, she must satisfy the following criteria. The subject is not of childbearing potential and satisfies any of the following criteria.

  * The subject is post-menopausal (absence of menses for at least 1 year).
  * The subject is surgically sterile.

The subject is of childbearing potential but satisfies all of the following criteria:

* The subject agrees not to get pregnant to 28 days after the last dose of the study drug.
* The subject has a negative pregnancy test. The subject agrees to use two of the established contraceptive methods listed below to 28 days after the last dose of the study drug when having heterosexual intercourse.

  * If the subject is a female, she must agree not to breastfeed to 28 days after the last dose of the study drug.
  * If the subject is a female, she must agree not to donate their eggs during the period from the assessment to 28 days after the last dose of the study drug.
  * In case a male subject's spouse or partner is of childbearing potential, the subject must agree to use two of the established contraceptive methods to 28 days after the last dose of the study drug.
  * If the subject is a male, he must agree not to donate their sperm to 28 days after the last dose of the study drug.

Exclusion Criteria:

* The subject has type 1 diabetes mellitus.
* The subject has any symptom of dysuria, anuria, oliguria or urinary retention.
* The subject has proliferative retinopathy.
* The subject has diabetic ketoacidosis.
* The subject has a history or complication of medically significant renal disease such as renovascular occlusive disease, nephrectomy and/or renal transplant.
* The subject has a history of recurrent urinary tract infection.
* The subject has symptomatic urinary tract infection or symptomatic genital infection.
* The subject has chronic disease(s) that require the continuous use of corticosteroids, immunosuppressants, etc.
* The subject has a history of cerebral vascular attack, unstable angina, myocardial infarction, vascular intervention, and serious heart disease within 1 year (52 weeks) before signing of the informed consent.
* The subject has a complication or surgical history of serious gastrointestinal disorder.
* The subject has severe hepatic dysfunction.
* The subject has uncontrolled blood pressure.
* The subject has unstable psychiatric disorder.
* The subject has severe infection or serious trauma, or perioperative.
* The subject has drug addiction or alcohol abuse.
* The subject has a history of malignant tumors.
* The subject has a history of an allergy to ipragliflozin and/or similar drugs (drugs possessing SGLT2 inhibitory action).
* The subject has used SGLT2 inhibitors, GLP-1 receptor agonists, sulfonylureas (SU), glinide agents, or insulin products other than long-acting insulin within 12 weeks before signing of the informed consent.

Primary outcomes:
measure: Change from baseline in insulin dose
timeFrame: Baseline and Week 24
measure: Percent change from baseline in insulin dose
timeFrame: Baseline and Week 24
Secondary outcomes:
measure: Change from baseline in insulin dose
timeFrame: Baseline and Week 0, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20 and the last assessment during the treatment period (up to Week 24)
measure: Percent change from baseline in insulin dose
timeFrame: Baseline and Week 0, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20 and the last assessment during the treatment period (up to Week 24)
measure: Change from baseline in HbA1c
timeFrame: Baseline and Week 0, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and the last assessment during the treatment period (up to Week 24)
measure: Change from baseline in fasting plasma glucose
timeFrame: Baseline and Week 0, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and the last assessment during the treatment period (up to Week 24)
measure: Change from baseline in cholesterol
timeFrame: Baseline and Week 0, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and the last assessment during the treatment period (up to Week 24)
measure: Change from baseline in glycoalbumin
timeFrame: Baseline and Week 0, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and the last assessment during the treatment period (up to Week 24)
measure: Change from baseline in leptin
timeFrame: Baseline and Week 0, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and the last assessment during the treatment period (up to Week 24)
measure: Change from baseline in adiponectin
timeFrame: Baseline and Week 0, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and the last assessment during the treatment period (up to Week 24)
measure: Change from baseline in glucagon
timeFrame: Baseline and Week 0, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and the last assessment during the treatment period (up to Week 24)
measure: Change from baseline in C-peptide
timeFrame: Baseline and Week 0, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and the last assessment during the treatment period (up to Week 24)
measure: Change from baseline in body weight
timeFrame: Baseline and Week 0, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and the last assessment during the treatment period (up to Week 24)
measure: Change from baseline in waist circumference
timeFrame: Baseline and Week 0, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and the last assessment during the treatment period (up to Week 24)
measure: Change from baseline in blood pressure
timeFrame: Baseline and Week 0, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and the last assessment during the treatment period (up to Week 24)
measure: Change from baseline in DTSQ
timeFrame: Baseline and Week 24 and the last assessment during the treatment period (up to Week 24)
measure: Number of subjects achieving withdrawal of insulin therapy
timeFrame: Up to Week 24
measure: Percent of subjects achieving withdrawal of insulin therapy
timeFrame: Up to Week 24
measure: Safety assessed by incidence of Adverse events
timeFrame: Up to Week 24
measure: Safety assessed by blood pressure in a sitting position
timeFrame: Up to Week 24
measure: Safety assessed by pulse rate in a sitting position
timeFrame: Up to Week 24
measure: Safety assessed by Hematology
timeFrame: Up to Week 24
measure: Safety assessed by biochemistry
timeFrame: Up to Week 24
Other outcomes:
Locations:
city: Gunma
country: Japan
facility: Site JP00007
city: Hiroshima
country: Japan
facility: Site JP00008
city: Hyogo
country: Japan
facility: Site JP00009
city: Kanagawa
country: Japan
facility: Site JP00010
city: Mie
country: Japan
facility: Site JP00003
city: Osaka
country: Japan
facility: Site JP00004
city: Shiga
country: Japan
facility: Site JP00015
city: Tochigi
country: Japan
facility: Site JP00002
city: Tochigi
country: Japan
facility: Site JP00005
city: Tochigi
country: Japan
facility: Site JP00013
city: Tokyo
country: Japan
facility: Site JP00001
city: Tokyo
country: Japan
facility: Site JP00006
city: Tokyo
country: Japan
facility: Site JP00011
city: Tokyo
country: Japan
facility: Site JP00012
city: Tokyo
country: Japan
facility: Site JP00014
Study officials:
affiliation: Astellas Pharma Inc
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Ishihara H, Yamaguchi S, Sugitani T, Kosakai Y. Open-Label Study to Assess the Efficacy of Ipragliflozin for Reducing Insulin Dose in Patients with Type 2 Diabetes Mellitus Receiving Insulin Therapy. Clin Drug Investig. 2019 Dec;39(12):1213-1221. doi: 10.1007/s40261-019-00851-z.