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

August 21, 2017 updated by: Astellas Pharma Europe B.V.

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)

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.

Study Overview

Status

Completed

Intervention / Treatment

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%).

Study Type

Interventional

Enrollment (Actual)

44

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

35 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part A
Ipragliflozin (low dose) & Placebo
Oral
Oral
Other Names:
  • Ipragliflozin
Experimental: Part B
Ipragliflozin (high dose)
Oral
Other Names:
  • Ipragliflozin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
4 days
Part A: Assessment of peripheral glucose utilization after an oral glucose load, following multiple doses of ipragliflozin
Time Frame: 4 days
4 days
Part A: Assessment of splanchnic uptake after an oral glucose load, following multiple doses of ipragliflozin
Time Frame: 4 days
4 days
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
4 days
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)
6 days (PK), 12 days (urine) and 8 days (PD)

Secondary Outcome Measures

Outcome Measure
Time Frame
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
4 days (sodium) and 14 days (glucose) days
Part A: Assessment of energy production and utilization of energy sources following multiple doses of ipragliflozin
Time Frame: 4 days
4 days
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
Up to 21 days
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
Up to 21 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 27, 2011

Primary Completion (Actual)

February 3, 2012

Study Completion (Actual)

February 3, 2012

Study Registration Dates

First Submitted

May 31, 2012

First Submitted That Met QC Criteria

May 31, 2012

First Posted (Estimate)

June 5, 2012

Study Record Updates

Last Update Posted (Actual)

August 22, 2017

Last Update Submitted That Met QC Criteria

August 21, 2017

Last Verified

August 1, 2017

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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