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

Type 1 Diabetes Mellitus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02529449
• Other study ID #: 1941-CL-6001
• Status: Completed
• Phase: Phase 2
• Start date: September 1, 2015
• Est. completion date: March 19, 2016

Study information

• Verified date: March 2019
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 43
• Est. completion date: March 19, 2016
• Est. primary completion date: March 19, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 74 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes Mellitus

Intervention

Drug:
• Placebo
Oral
• ASP1941
Oral

Locations

Country	Name	City	State
Japan	Site JP00006	Aichi
Japan	Site JP00002	Fukuoka
Japan	Site JP00009	Gunma
Japan	Site JP00001	Ibaraki
Japan	Site JP00005	Kanagawa
Japan	Site JP00008	Kanagawa
Japan	Site JP00003	Okayama
Japan	Site JP00004	Osaka
Japan	Site JP00010	Osaka
Japan	Site JP00011	Osaka
Japan	Site JP00007	Tokyo

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma Inc

Country where clinical trial is conducted

Japan, 

Outcome

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

External Links

•   Link to results on the Astellas Clinical Study Results website