A Phase 1 Study to Investigate the Mechanism of Action of Ipragliflozin

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Europe B.V. )
ClinicalTrials.gov Identifier:
NCT01611363
First received: May 31, 2012
Last updated: NA
Last verified: May 2012
History: No changes posted
  Purpose

In this study the effect of ipragliflozin on glucose homeostasis in healthy subjects and T2DM subjects, and the effect of exposure of ipragliflozin on urinary glucose excretion and plasma glucose in T2DM subjects will be investigated.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: ASP1941
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: An Exploratory Study to Investigate the Effects of Ipragliflozin (ASP1941) on Glucose Homeostasis and Urinary Glucose Excretion in Healthy Subjects and Subjects With Type 2 Diabetes Mellitus (T2DM)

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Part A: Assessment of glucose homeostasis in fasted condition and after an oral glucose load, following multiple doses of ipragliflozin in healthy subjects and subjects with T2DM [ Time Frame: 4 days ] [ Designated as safety issue: No ]
  • Part A: Assessment of peripheral glucose utilization after an oral glucose load, following multiple doses of ipragliflozin [ Time Frame: 4 days ] [ Designated as safety issue: No ]
  • Part A: Assessment of splanchnic uptake after an oral glucose load, following multiple doses of ipragliflozin [ Time Frame: 4 days ] [ Designated as safety issue: No ]
  • Part A: Assessment of mean glucose levels in fasted condition and after an oral glucose load, following multiple doses of ipragliflozin [ Time Frame: 4 days ] [ Designated as safety issue: No ]
  • Part B: Assessment of the relationship between the exposure to ipragliflozin in plasma, urinary glucose excretion and plasma glucose levels in subjects with T2DM [ Time Frame: 6 days (PK), 12 days (urine) and 8 days (PD) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Part A: Assessment of steady state urinary sodium excretion and urinary glucose excretion following multiple doses of ipragliflozin [ Time Frame: 4 days (sodium) and 14 days (glucose) days ] [ Designated as safety issue: No ]
  • Part A: Assessment of energy production and utilization of energy sources following multiple doses of ipragliflozin [ Time Frame: 4 days ] [ Designated as safety issue: No ]
  • Part A: Safety and tolerability following multiple doses of ipragliflozin assessed by recording adverse events, laboratory assessments, vital signs, electrocardiograms (ECGs) and signs and symptoms of hypoglycemia [ Time Frame: Up to 21 days ] [ Designated as safety issue: No ]
  • Part B: Safety and tolerability following multiple doses of ipragliflozin assessed by recording adverse events, laboratory assessments, vital signs, electrocardiograms (ECGs) and signs and symptoms of hypoglycemia [ Time Frame: Up to 21 days ] [ Designated as safety issue: No ]

Enrollment: 44
Study Start Date: October 2011
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part A
Ipragliflozin (low dose) & Placebo
Drug: ASP1941
Oral
Other Name: Ipragliflozin
Drug: Placebo
Oral
Experimental: Part B
Ipragliflozin (high dose)
Drug: ASP1941
Oral
Other Name: Ipragliflozin

Detailed Description:

This study will consist of 2 parts. In Part A the effect of ipragliflozin on the glucose homeostasis will be investigated and in Part B we will investigate the effect of exposure of ipragliflozin on UGE and plasma glucose levels.

Part A This part will be a randomized, double-blind, placebo-controlled, 2- period, 2 treatment crossover design in healthy subjects and in T2DM subjects who are drug naïve or washed out for metformin prior to admission to the clinical site.

Part B This part will be an open-label, randomized, 2-period, 2 treatment crossover design in T2DM subjects stratified by baseline HbA1c levels (6.0-6.9%, 7.0-7.9%, 8.0-8.9% or 9.0-9.9%).

  Eligibility

Ages Eligible for Study:   35 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Inclusion Part A: Healthy subjects

  • Subject is healthy without diabetes mellitus
  • Subject has a fasted plasma glucose (FPG) of less than 5.6 mmol/l at screening
  • Subject has a Body Mass Index (BMI) more than or equal to 18.5 and less than 28.0 kg/m2
  • Subject's serum creatinine is within the normal range

Inclusion Part A: T2DM subjects

  • Subject has been diagnosed with T2DM for at least 6 months
  • Subject's body mass index (BMI) is equal to or more than 20.0 and less than 35.0 kg/m2 at screening
  • Subject has a HbA1c level above 7.0% and less than 9.0% at screening
  • Subject has a (FPG) of less than 10.0 mmol/l
  • Subject is treatment naïve to glucose-lowering medication or uses metformin that will be washed out at least 3 weeks prior to the first dosing at Day 1
  • Subject's serum creatinine is within the normal range

Inclusion Part B: T2DM subjects

  • Subject has a body mass index (BMI) of more than or equal to 20.0 and less than 35.0 kg/m2 at screening.
  • Subject has been diagnosed with T2DM for at least 6 months
  • Subject has HbA1c level of equal to or more than 6.0% and less than 10% at screening
  • Subject has a FPG of less than 10.0 mmol/l
  • Subject is drug naïve or on a stable glucose lowering therapy (metformin, TZD, DPP-4 inhibitor or SUD therapy

Exclusion Criteria:

Exclusion Part A: Healthy subjects

  • Any of the liver function tests above the upper limit of normal
  • A QTc interval of >430 ms (males) and >450 ms (females), a history of unexplained syncope, cardiac arrest, unexplained significant cardiac arrhythmias or torsades de pointes, structural heart disease, or a family history of Long QT Syndrome (LQTS)
  • Abnormal pulse and/or blood pressure measurements at screening as follows: Pulse <40 or >90 bpm; mean systolic blood pressure >140 mmHg; mean diastolic blood pressure >90 mmHg
  • eGFR (based on Modification of Diet in Renal Disease (MDRD) method) less than 60 ml/min/1.73m2 on Day -2

Exclusion Part A & Part B: T2DM subjects

  • Subject has type 1 diabetes mellitus
  • A QTc interval of >450 ms (males) and >470 ms (females), a history of unexplained syncope, cardiac arrest, unexplained significant cardiac arrhythmias or torsades de pointes, structural heart disease, or a family history of Long QT Syndrome (LQTS)
  • Subject is on an insulin therapy or has received insulin within 3 months prior to screening, with the exception of acute use of <7 days prior to screening
  • Subject has a urinary microalbumin/creatinine ratio above or equal to 300 mg/g at screening
  • Subject has an ALT and/or AST higher than 3 times the upper limit of normal or has a total bilirubin more than 2 times the upper limit of normal at screening
  • Subject has a symptomatic urinary tract infection or symptomatic genito-urinary infection at screening
  • Subject has persistent, uncontrolled severe hypertension as indicated by a mean systolic blood pressure > 160 mmHg or a mean diastolic blood pressure of > 100 mmHg
  • Subject has significant cardiovascular disease
  • eGFR (based on MDRD method) less than 60 ml/min/1.73m2 on Day -2
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01611363

Locations
Germany
Neuss, Germany, 41460
Sponsors and Collaborators
Astellas Pharma Europe B.V.
Investigators
Study Director: Clinical Study Manager Astellas Pharma Europe B.V.
  More Information

No publications provided

Responsible Party: Astellas Pharma Inc ( Astellas Pharma Europe B.V. )
ClinicalTrials.gov Identifier: NCT01611363     History of Changes
Other Study ID Numbers: 1941-CL-0050, 2010-024070-19
Study First Received: May 31, 2012
Last Updated: May 31, 2012
Health Authority: Germany: German Institute of Medical Documentation and Information

Keywords provided by Astellas Pharma Inc:
Phase 1
Diabetes Mellitus
Healthy
Ipragliflozin
Pharmacokinetics
Pharmacodynamics

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on August 21, 2014