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

Primary Purpose

Type 2 Diabetes Mellitus

Status

Completed

Phase

Phase 1

Locations

Germany

Study Type

Interventional

Intervention

ASP1941

Placebo

About this trial

This is an interventional basic science trial for Type 2 Diabetes Mellitus focused on measuring Ipragliflozin, Phase 1, Healthy, Diabetes Mellitus, Pharmacokinetics, Pharmacodynamics

Eligibility Criteria

35 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Part A

Part B

Arm Description

Ipragliflozin (low dose) & Placebo

Ipragliflozin (high dose)

Outcomes

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

Part A: Assessment of peripheral glucose utilization after an oral glucose load, following multiple doses of ipragliflozin

Part A: Assessment of splanchnic uptake after an oral glucose load, following multiple doses of ipragliflozin

Part A: Assessment of mean glucose levels in fasted condition and after an oral glucose load, following multiple doses of ipragliflozin

Part B: Assessment of the relationship between the exposure to ipragliflozin in plasma, urinary glucose excretion and plasma glucose levels in subjects with T2DM

Secondary Outcome Measures

Part A: Assessment of steady state urinary sodium excretion and urinary glucose excretion following multiple doses of ipragliflozin

Part A: Assessment of energy production and utilization of energy sources following multiple doses of ipragliflozin

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

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

Full Information

NCT ID

NCT01611363

First Posted

May 31, 2012

Last Updated

August 21, 2017

Sponsor

Astellas Pharma Europe B.V.

1. Study Identification

Unique Protocol Identification Number

NCT01611363

Brief Title

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

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)

Study Type

Interventional

2. Study Status

Record Verification Date

August 2017

Overall Recruitment Status

Completed

Study Start Date

October 27, 2011 (Actual)

Primary Completion Date

February 3, 2012 (Actual)

Study Completion Date

February 3, 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Astellas Pharma Europe B.V.

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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.

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%).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type 2 Diabetes Mellitus

Keywords

Ipragliflozin, Phase 1, Healthy, Diabetes Mellitus, Pharmacokinetics, Pharmacodynamics

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

44 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part A

Arm Type

Experimental

Arm Description

Ipragliflozin (low dose) & Placebo

Arm Title

Part B

Arm Type

Experimental

Arm Description

Ipragliflozin (high dose)

Intervention Type

Drug

Intervention Name(s)

ASP1941

Other Intervention Name(s)

Ipragliflozin

Intervention Description

Oral

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Oral

Primary Outcome Measure Information:

Title

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

Title

Part A: Assessment of peripheral glucose utilization after an oral glucose load, following multiple doses of ipragliflozin

Time Frame

4 days

Title

Part A: Assessment of splanchnic uptake after an oral glucose load, following multiple doses of ipragliflozin

Time Frame

4 days

Title

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

Title

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)

Secondary Outcome Measure Information:

Title

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

Title

Part A: Assessment of energy production and utilization of energy sources following multiple doses of ipragliflozin

Time Frame

4 days

Title

Time Frame

Up to 21 days

Title

Time Frame

Up to 21 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

35 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Study Manager

Organizational Affiliation

Astellas Pharma Europe B.V.

Official's Role

Study Director

Facility Information:

City

Neuss

ZIP/Postal Code

41460

Country

Germany

12. IPD Sharing Statement

Links:

URL

https://www.astellasclinicalstudyresults.com/study.aspx?ID=4

Description

Link to results on Astellas Clinical Study Results website

Learn more about this trial

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

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