Pharmacodynamics, Pharmacokinetics, and Safety of ASP1941 in Patients With Type 1 Diabetes Mellitus

Study Overview
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Brief Summary
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The objective of this study is to assess pharmacodynamics, pharmacokinetics, and safety of ASP1941 in patients with type 1 diabetes mellitus when administered once daily (q.d.) for 2 weeks.

Official Title
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A Phase 2, Clinical Pharmacological Study of ASP1941 in Japanese Patients With Type 1 Diabetes Mellitus

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Drug: Placebo
* Drug: ASP1941


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At the time of obtaining informed consent: Subject is diagnosed with type 1 diabetes mellitus and has been treated with insulin therapy for at least 52 weeks (364 days). Subject is able to be admitted to the site as scheduled. Subject is able to record in Patient's diary from the first study drug dose in observation period until the day before the end of post observation. At screening period: Subject has an HbA1c (NGSP) value of between 7.5% and 10.0%. If subject has an HbA1c value of between 7.3% and 10.2% (out of the reference range), HbA1c may be re-measured only once within the allowance range in screening period. Re-measured HbA1c (NGSP) value will be adopted for the determination. Subject has been receiving insulin therapy at daily doses (instructed by a doctor) within a ±20% range for at least 12weeks (83days) prior to the start of screening. Subject has a fasting serum C-peptide level ≤0.5 ng/mL at screening. Subject receives treatments for complications (except for transient diseases such as a cold) that, in the investigator's or sub-investigator's opinion, need not to be changed during the period from the start of screening to the end of the treatment period. Subject has body mass index (BMI) value of 20.0 to 35.0 kg/m2 at screening. Exclusion Criteria: At the time of obtaining informed consent: Subject has type 2 diabetes mellitus. Subject has participated or has been participating in a clinical study or a post marketing study of another drug or medical equipment within 12 weeks (84 days) prior to obtaining informed consent. Subject has received ASP1941 (ipragliflozin) with the exception of placebo. At screening period: Subject has proliferative retinopathy (subjects with stable condition after photocoagulation etc. may be enrolled in the study). Subject has developed hypoglycemia unawareness (requires help of a third person) or severe hypoglycemia (diabetic coma, precoma, or convulsion) within 12 weeks (84 days) prior to the start of screening. Subject has developed diabetic ketoacidosis within 12 weeks (84 days) prior to the start of screening. Subject has chronic disease(s) which require the continuous use of corticosteroids or immunosuppressants (oral administration, injection, inhalation, or suppository). Subject has received hypoglycemic agent(s) other than insulin within 12 weeks (83 days) prior to the start of screening. Subject with perioperative, severe infection or serious injury. Subject whose serum creatinine value exceeds the upper limit of normal range at screening. Subject has a urinary albumin/urinary creatinine ratio>300 mg/g in urinalysis at screening. Subject has a history of clinically significant renal disease(s) such as renovascular occlusive disease, nephrectomy, and/or renal transplant. Subject has AST and ALT >2 ×ULN or T-Bil >1.5 × ULN at screening, or has a history of serious hepatic diseases. Subject presents with symptoms of dysuria, anuria, oliguria and urinary retention. Subject has a history of recurrent urinary tract infections and recurrent genital infections (developed 3 times or more within 24 weeks (168 days) prior to the start of screening). Subject has urinary tract infection or genital infection with subjective symptoms. Subject has a history of angina unstable, myocardial infarction, angioplasty, and serious heart disease (NYHA Class II-IV) within 24 weeks (168 days) prior to the start of screening, or has complications of heart disease that, in the investigator's or sub-investigator's opinion, may interfere with the evaluation of safety of ASP1941. Subject has uncontrolled blood pressure (systolic blood pressure≥160 mmHg or diastolic blood pressure≥100 mmHg in the supine position after a 5-minute rest at screening ). Subject has serious gastrointestinal disease or a history of serious gastrointestinal operation. Subject has malignant tumors concomitantly (subject may be enrolled in the study if the subject has a history of a malignant tumor which has not recurred without any treatment within 5 years prior to the start of screening). Subject has psychiatric disorder that makes the subject unsuitable for study participation. Subject has drug addiction or alcohol abuse. Subject has a history of drug allergies. Subject is unable to adhere to any of the compliance such as hospital visits and dose instruction specified in this study, or does not agree with it. Subject has donated 400 mL of whole blood within 90 days, 200 mL of whole blood within 30 days, or blood components within 14 days prior to the start of screening. Subject has any condition that, in the investigator's or sub-investigator's opinion, makes the subject unsuitable for study participation.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>once daily | Drug: Placebo<br>* Oral<br>|
| Experimental: ASP1941 Low dose group<br>once daily | Drug: ASP1941<br>* Oral<br>* Other names: Ipragliflozin;|
| Experimental: ASP1941 Middle dose group<br>once daily | Drug: ASP1941<br>* Oral<br>* Other names: Ipragliflozin;|
| Experimental: ASP1941 High dose group<br>once daily | Drug: ASP1941<br>* Oral<br>* Other names: Ipragliflozin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Daily profile of plasma glucose levels |  | up to Day 14 | 
| Area under the concentration-time curve (AUC) 0-24hr (AUC0-24h) of plasma glucose levels |  | at Day -1, Day 1 and Day 14 | 
| AUC0-3h of plasma glucose levels |  | at Day -1, Day 1 and Day 14 | 
| AUC0-4h of plasma glucose levels |  | up to Day 14 | 
| AUC0-10h of plasma glucose levels |  | up to Day 14 | 
| Fasting plasma glucose levels |  | up to Day 21 | 
| Glycoalbumin |  | up to Day 21 | 
| Urinary glucose excretion |  | up to Day 14 | 
| Urinary glucose excretion rate |  | up to Day 14 | 
| Urine volume |  | up to Day 14 | 
| Urinary glucose concentration |  | up to Day 15 | 
| Body weight |  | up to Day 21 | 
| Renal glucose clearance |  | up to Day 14 | 
| Plasma concentration of unchanged ASP1941 |  | up to Day 14 | 
| Urinary concentration of unchanged ASP1941 |  | up to Day 14 | 
| Pharmacokinetics (PK) parameter of ASP1941 in plasma: AUC from time 0 extrapolated to infinity (AUCinf) |  | at Day 1 | 
| PK parameter of ASP1941 in plasma: AUC from the time of dosing to the last measurable concentration (AUClast) |  | at Day 1 and Day 14 | 
| PK parameter of ASP1941 in plasma: AUC from the time of dosing to 24 hr (AUC0-24h) |  | at Day 1 and Day 14 | 
| PK parameter of ASP1941 in plasma: Oral Clearance (CL/F) |  | at Day 1 and Day 14 | 
| PK parameter of ASP1941 in plasma: Maximum concentration (Cmax) |  | at Day 1 and Day 14 | 
| PK parameter of ASP1941 in plasma: Terminal Elimination Half-life (t1/2) |  | at Day 1 and Day 14 | 
| PK parameter of ASP1941 in plasma: Time of the Maximum Concentration (tmax) |  | at Day 1 and Day 14 | 
| PK parameter of ASP1941 in urine: Amount excreted in urine between time (Ae) |  | at Day 1 and Day 14 | 
| PK parameter of ASP1941 in urine: % of the dose of excreted in urine (Ae%) |  | at Day 1 and Day 14 | 
| PK parameter of ASP1941 in plasma and urine: Renal Clearance (CLr) |  | at Day 1 and Day 14 | 
| Safety assessed by vital signs | Supine blood pressure and supine pulse rate | up to Day 21 | 
| Safety assessed by 12-lead electrocardiogram |  | up to Day 21 | 
| Safety assessed by laboratory tests | Hematology, biochemistry and urinalysis | up to Day 21 | 
| Safety assessed by self-monitored blood glucose levels |  | up to Day 21 | 
| Safety assessed by Adverse events |  | up to Day 21 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ASP1941, type 1 diabetes mellitus, SGLT2 inhibitor