Clinical trial NCT02529449: Pharmacodynamics, Pharmacokinetics, and Safety of ASP1941 in Patients With Type 1 Diabetes Mellitus
Official title: A Phase 2, Clinical Pharmacological Study of ASP1941 in Japanese Patients With Type 1 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 1 Diabetes Mellitus
Keywords: ASP1941
type 1 diabetes mellitus
SGLT2 inhibitor
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2015-08-20
Enrollment: 43
Sex: ALL
Minimum age (years): 20
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Daily profile of plasma glucose levels
timeFrame: up to Day 14
measure: Area under the concentration-time curve (AUC) 0-24hr (AUC0-24h) of plasma glucose levels
timeFrame: at Day -1, Day 1 and Day 14
measure: AUC0-3h of plasma glucose levels
timeFrame: at Day -1, Day 1 and Day 14
measure: AUC0-4h of plasma glucose levels
timeFrame: up to Day 14
measure: AUC0-10h of plasma glucose levels
timeFrame: up to Day 14
measure: Fasting plasma glucose levels
timeFrame: up to Day 21
measure: Glycoalbumin
timeFrame: up to Day 21
measure: Urinary glucose excretion
timeFrame: up to Day 14
measure: Urinary glucose excretion rate
timeFrame: up to Day 14
measure: Urine volume
timeFrame: up to Day 14
measure: Urinary glucose concentration
timeFrame: up to Day 15
measure: Body weight
timeFrame: up to Day 21
measure: Renal glucose clearance
timeFrame: up to Day 14
measure: Plasma concentration of unchanged ASP1941
timeFrame: up to Day 14
measure: Urinary concentration of unchanged ASP1941
timeFrame: up to Day 14
measure: Pharmacokinetics (PK) parameter of ASP1941 in plasma: AUC from time 0 extrapolated to infinity (AUCinf)
timeFrame: at Day 1
measure: PK parameter of ASP1941 in plasma: AUC from the time of dosing to the last measurable concentration (AUClast)
timeFrame: at Day 1 and Day 14
measure: PK parameter of ASP1941 in plasma: AUC from the time of dosing to 24 hr (AUC0-24h)
timeFrame: at Day 1 and Day 14
measure: PK parameter of ASP1941 in plasma: Oral Clearance (CL/F)
timeFrame: at Day 1 and Day 14
measure: PK parameter of ASP1941 in plasma: Maximum concentration (Cmax)
timeFrame: at Day 1 and Day 14
measure: PK parameter of ASP1941 in plasma: Terminal Elimination Half-life (t1/2)
timeFrame: at Day 1 and Day 14
measure: PK parameter of ASP1941 in plasma: Time of the Maximum Concentration (tmax)
timeFrame: at Day 1 and Day 14
measure: PK parameter of ASP1941 in urine: Amount excreted in urine between time (Ae)
timeFrame: at Day 1 and Day 14
measure: PK parameter of ASP1941 in urine: % of the dose of excreted in urine (Ae%)
timeFrame: at Day 1 and Day 14
measure: PK parameter of ASP1941 in plasma and urine: Renal Clearance (CLr)
timeFrame: at Day 1 and Day 14
measure: Safety assessed by vital signs
timeFrame: up to Day 21
measure: Safety assessed by 12-lead electrocardiogram
timeFrame: up to Day 21
measure: Safety assessed by laboratory tests
timeFrame: up to Day 21
measure: Safety assessed by self-monitored blood glucose levels
timeFrame: up to Day 21
measure: Safety assessed by Adverse events
timeFrame: up to Day 21
Secondary outcomes:
Other outcomes:
Locations:
city: Aichi
country: Japan
facility: Site JP00006
city: Fukuoka
country: Japan
facility: Site JP00002
city: Gunma
country: Japan
facility: Site JP00009
city: Ibaraki
country: Japan
facility: Site JP00001
city: Kanagawa
country: Japan
facility: Site JP00005
city: Kanagawa
country: Japan
facility: Site JP00008
city: Okayama
country: Japan
facility: Site JP00003
city: Osaka
country: Japan
facility: Site JP00004
city: Osaka
country: Japan
facility: Site JP00010
city: Osaka
country: Japan
facility: Site JP00011
city: Tokyo
country: Japan
facility: Site JP00007
Study officials:
affiliation: Astellas Pharma Inc
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Toyoshima J, Saito M, Kaibara A, Isaka H, Sakatani T. Comparison of the Pharmacokinetic and Pharmacodynamic Relationship of Ipragliflozin Between Patients With Type 1 and Type 2 Diabetes Mellitus. Clin Ther. 2020 Sep;42(9):1787-1798.e3. doi: 10.1016/j.clinthera.2020.07.009. Epub 2020 Aug 21.