Clinical trial NCT02201004: TOFO Insulin Combination Trial
Official title: A Randomized, Double Blind Placebo Controlled 2-Arm Parallel Group, Multicenter Study With A 16-Week Treatment Assessing The Efficacy And Safety, And 52-Week Long Term Safety Including 36-Week Open Label Extension Of Tofogliflozin With Insulin Treatment In Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Kowa Company, Ltd.
First posted: 2014-07-25
Enrollment: 211
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Primary Objectives:

To assess the effects of tofogliflozin on glycemic control in comparison to placebo as an add-on treatment to insulin treatment in terms of glycated hemoglobin (HbA1c) reduction over a period of 16 weeks in patients with type 2 diabetes mellitus.

To assess the safety of tofogliflozin in combination with insulin treatment throughout 52 weeks.

Secondary Objectives:

To assess the effects of tofogliflozin in comparison to placebo on:

* Body weight
* Fasting plasma glucose (FPG)
* Postprandial plasma glucose (PPG) To assess the long term safety and tolerability of tofogliflozin.

Detailed description: The total study duration from screening for a patient can be approximately up to 1 year, including a screening period of 2 weeks, double-blinded placebo controlled treatment period of 16 weeks, an open-labeled extension period of 36 weeks, and a follow-up period of 3 days.

Eligibility criteria: Inclusion criteria:

* Patients aged 20-75 years old with type 2 diabetes mellitus (T2DM).
* Hemoglobin A1c ≥7.5% - ≤10.5% and FPG ≤220 mg/dL.
* Basal bolus (BB), Bolus, Premix, Basal supported oral therapy (BOT) regimens used for more than 12 weeks before screening.
* Stable dose (-/+20%) of insulin and no change in the dose of oral hypoglycemic agents for more than 12 weeks before screening.
* Only Dipeptidyl peptidase-4 inhibitor is allowed for basal supported oral therapy (BOT) regimen.
* Body mass index (BMI) ≥18.5 kg/m\^2 and \<35.0 kg/m\^2.
* No change of antihypertensive, anti-hypercholesterolemia and uric acid lowering drug 4 weeks before screening.

Exclusion criteria:

* Type 1 diabetes mellitus.
* Pregnancy or lactation.
* Severely uncontrolled glycemic situation.
* History of metabolic acidosis, including diabetic ketoacidosis, within 1 year prior to screening.
* History of myocardial infarction, stroke, or heart failure requiring hospitalization or drug or alcohol abuse within the previous 6 months.
* A measured serum creatinine level greater than 2.0 mg/dL for men and 1.5 mg/dL for women.
* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥2.5 times the upper limit of the reference range at the central laboratory test facility.
* Has previously received treatment with the investigational product.
* Has received treatment with another investigational product or non-approved drug within 3 months before tests for provisional enrolment.
* Corticosteroid therapy for 14 or more days in total within 8 weeks before tests for provisional enrolment (excluding those used for localized effects, such as drugs for topical \[skin\] application, eye drops and sprays).
* Patients who are frequently experiencing orthostatic hypotension.
* Required a change in the dosing regimen for the following drugs within 4 weeks before tests for provisional enrolment:
* Lipid-lowering drug
* Antihypertensive drug
* Thyroid hormone preparation
* Uric acid lowering drug

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Primary outcomes:
measure: Change in HbA1c from baseline
timeFrame: 16 weeks after first intake of investigational product
Secondary outcomes:
measure: Change of Body Weight (BW) from baseline
timeFrame: 16 weeks after first intake of investigational product
measure: Change of FPG from baseline
timeFrame: 16 weeks after first intake of investigational product
measure: Change of PPG from baseline
timeFrame: 16 weeks after first intake of investigational product
measure: Number of subjects with adverse events
timeFrame: Up to 52 weeks from the first intake of investigational medicinal product
Other outcomes:
Locations:
city: Adachi-ku
country: Japan
facility: Investigational Site Number 392-028
city: Atsugi-shi
country: Japan
facility: Investigational Site Number 392-007
city: Chuoh-ku
country: Japan
facility: Investigational Site Number 392-026
city: Fukuoka-shi
country: Japan
facility: Investigational Site Number 392-021
city: Ichihara-shi
country: Japan
facility: Investigational Site Number 392-002
city: Iruma-shi
country: Japan
facility: Investigational Site Number 392-012
city: Kawaguchi-shi
country: Japan
facility: Investigational Site Number 392-003
city: Kitakyusyu-shi
country: Japan
facility: Investigational Site Number 392-014
city: Kobe-shi
country: Japan
facility: Investigational Site Number 392-027
city: Koga-shi
country: Japan
facility: Investigational Site Number 392-004
city: Kunitachi-shi
country: Japan
facility: Investigational Site Number 392-022
city: Kurume-shi
country: Japan
facility: Investigational Site Number 392-019
city: Kyoto-shi
country: Japan
facility: Investigational Site Number 392-001
city: Kyoto-shi
country: Japan
facility: Investigational Site Number 392-024
city: Matsudo-shi
country: Japan
facility: Investigational Site Number 392-006
city: Mito-shi
country: Japan
facility: Investigational Site Number 392-008
city: Musashino-shi
country: Japan
facility: Investigational Site Number 392-030
city: Okayama-shi
country: Japan
facility: Investigational Site Number 392-029
city: Otsu-shi
country: Japan
facility: Investigational Site Number 392-017
city: Sagamihara-shi
country: Japan
facility: Investigational Site Number 392-011
city: Sakai-shi
country: Japan
facility: Investigational Site Number 392-020
city: Sapporo-shi
country: Japan
facility: Investigational Site Number 392-010
city: Sendai-shi
country: Japan
facility: Investigational Site Number 392-016
city: Shinjuku-ku
country: Japan
facility: Investigational Site Number 392-018
city: Shizuoka-shi
country: Japan
facility: Investigational Site Number 392-005
city: Suita-shi
country: Japan
facility: Investigational Site Number 392-031
city: Sumida-ku
country: Japan
facility: Investigational Site Number 392-015
city: Sunto-gun
country: Japan
facility: Investigational Site Number 392-023
city: Tokorozawa-shi
country: Japan
facility: Investigational Site Number 392-013
city: Yokohama-shi
country: Japan
facility: Investigational Site Number 392-025
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Terauchi Y, Tamura M, Senda M, Gunji R, Kaku K. Efficacy and safety of tofogliflozin in Japanese patients with type 2 diabetes mellitus with inadequate glycaemic control on insulin therapy (J-STEP/INS): Results of a 16-week randomized, double-blind, placebo-controlled multicentre trial. Diabetes Obes Metab. 2017 Oct;19(10):1397-1407. doi: 10.1111/dom.12957. Epub 2017 Jul 13.