A Phase 2, Clinical Pharmacological Study of ASP1941 in Japanese Patients With Type 1 Diabetes Mellitus
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 43
- 试验地点
- 11
- 主要终点
- Urine volume
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 20 Years 至 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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 ASP
- •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.
研究组 & 干预措施
ASP1941 High dose group
once daily
干预措施: ASP1941 (Drug)
ASP1941 Low dose group
once daily
干预措施: ASP1941 (Drug)
ASP1941 Middle dose group
once daily
干预措施: ASP1941 (Drug)
Placebo
once daily
干预措施: Placebo (Drug)
结局指标
主要结局
Urine volume
时间窗: up to Day 14
Body weight
时间窗: up to Day 21
AUC0-3h of plasma glucose levels
时间窗: at Day -1, Day 1 and Day 14
Daily profile of plasma glucose levels
时间窗: up to Day 14
AUC0-4h of plasma glucose levels
时间窗: up to Day 14
AUC0-10h of plasma glucose levels
时间窗: up to Day 14
Urinary glucose excretion
时间窗: up to Day 14
Urinary concentration of unchanged ASP1941
时间窗: up to Day 14
Pharmacokinetics (PK) parameter of ASP1941 in plasma: AUC from time 0 extrapolated to infinity (AUCinf)
时间窗: at Day 1
PK parameter of ASP1941 in plasma: AUC from the time of dosing to the last measurable concentration (AUClast)
时间窗: at Day 1 and Day 14
PK parameter of ASP1941 in plasma: AUC from the time of dosing to 24 hr (AUC0-24h)
时间窗: at Day 1 and Day 14
PK parameter of ASP1941 in plasma: Oral Clearance (CL/F)
时间窗: at Day 1 and Day 14
PK parameter of ASP1941 in plasma: Maximum concentration (Cmax)
时间窗: at Day 1 and Day 14
PK parameter of ASP1941 in plasma: Terminal Elimination Half-life (t1/2)
时间窗: at Day 1 and Day 14
Glycoalbumin
时间窗: up to Day 21
Urinary glucose concentration
时间窗: up to Day 15
Renal glucose clearance
时间窗: up to Day 14
Plasma concentration of unchanged ASP1941
时间窗: up to Day 14
Area under the concentration-time curve (AUC) 0-24hr (AUC0-24h) of plasma glucose levels
时间窗: at Day -1, Day 1 and Day 14
Fasting plasma glucose levels
时间窗: up to Day 21
Urinary glucose excretion rate
时间窗: up to Day 14
PK parameter of ASP1941 in plasma: Time of the Maximum Concentration (tmax)
时间窗: at Day 1 and Day 14
PK parameter of ASP1941 in urine: Amount excreted in urine between time (Ae)
时间窗: at Day 1 and Day 14
PK parameter of ASP1941 in urine: % of the dose of excreted in urine (Ae%)
时间窗: at Day 1 and Day 14
PK parameter of ASP1941 in plasma and urine: Renal Clearance (CLr)
时间窗: at Day 1 and Day 14
Safety assessed by vital signs
时间窗: up to Day 21
Supine blood pressure and supine pulse rate
Safety assessed by 12-lead electrocardiogram
时间窗: up to Day 21
Safety assessed by laboratory tests
时间窗: up to Day 21
Hematology, biochemistry and urinalysis
Safety assessed by self-monitored blood glucose levels
时间窗: up to Day 21
Safety assessed by Adverse events
时间窗: up to Day 21
次要结局
未报告次要终点