A Study of the Effects of Canagliflozin on Plasma Volume in Patients With Type 2 Diabetes Mellitus

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01483781
First received: November 30, 2011
Last updated: August 19, 2014
Last verified: August 2014
  Purpose

The purpose of the study is to evaluate the effects of canagliflozin on plasma volume and renal parameters in patients with Type 2 Diabetes Mellitus who are currently taking metformin and being treated for high blood pressure.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Plasma Volume
Drug: Canagliflozin
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-Blind, Placebo-Controlled, Randomized, Parallel-Groups Study to Investigate the Effects of JNJ-28431754 (Canagliflozin) on Plasma Volume and Renal Function in Subjects With Type 2 Diabetes Mellitus

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • Change in plasma volume (PV) [ Time Frame: Baseline to Week 12 of the double-blind treatment period ] [ Designated as safety issue: No ]
    Baseline is defined as up to 3 days predose (Week -1)

  • Number of patients who experience at least 1 occurrence of a treatment-related adverse event [ Time Frame: Day 1 to Day 85 ] [ Designated as safety issue: No ]
    Treatment-related adverse events are adverse events with onset during the treatment phase.

  • Number of hypoglycemic events reported [ Time Frame: Baseline up to Day 98 ] [ Designated as safety issue: No ]
    Baseline is defined as up to 3 days predose (Week -1)

  • Change in electrocardiogram (ECG) parameters [ Time Frame: Baseline up to Day 98 ] [ Designated as safety issue: No ]
    Baseline is defined as up to 3 days predose (Week -1)

  • Change in blood pressure measurements [ Time Frame: Baseline up to Day 98 ] [ Designated as safety issue: No ]
    Baseline is defined as up to 3 days predose (Week -1)

  • Number of patients with physical examination findings reported as adverse events [ Time Frame: Baseline up to Week 12 ] [ Designated as safety issue: No ]
    Baseline is defined as up to 3 days predose (Week -1)

  • Change from baseline in pulse rate (beats/minute) [ Time Frame: Baseline up to Day 98 ] [ Designated as safety issue: No ]
    Baseline is defined as up to 3 days predose (Week -1)

  • Change in chemistry laboratory analytes [ Time Frame: Baseline up to Day 98 ] [ Designated as safety issue: No ]
    Baseline is defined as up to 3 days predose (Week -1)

  • Change from baseline in urinalysis laboratory analytes [ Time Frame: Baseline up to Day 98 ] [ Designated as safety issue: No ]
    Baseline is defined as up to 3 days predose (Week -1)

  • Change in hematology laboratory analytes [ Time Frame: Baseline up to Day 98 ] [ Designated as safety issue: No ]
    Baseline is defined as up to 3 days predose (Week -1)


Secondary Outcome Measures:
  • Change in PV [ Time Frame: Baseline to Week 1 of the double-blind treatment period ] [ Designated as safety issue: No ]
    Baseline is defined as up to 3 days predose (Week -1)

  • Change in body weight [ Time Frame: Baseline to approximately Week 1 and Week 12 of Double-Blind Treatment Phase ] [ Designated as safety issue: No ]
    Baseline is defined as up to 3 days predose (Week -1)

  • Change in 24-hour urine volume [ Time Frame: Baseline to approximately Week 1 and Week 12 of Double-Blind Treatment Phase ] [ Designated as safety issue: No ]
    Baseline is defined as up to 3 days predose (Week -1)

  • Change in 24-hour fractional and total excretion of uric acid [ Time Frame: Baseline to approximately Week 1 and Week 12 of Double-Blind Treatment Phase ] [ Designated as safety issue: No ]
    Baseline is defined as up to 3 days predose (Week -1)

  • Change in urine pH [ Time Frame: Baseline to approximately Week 1 and Week 12 of Double-Blind Treatment Phase ] [ Designated as safety issue: No ]
    Baseline is defined as up to 3 days predose (Week -1)

  • Change in percent Hemoglobin A1c (HbA1c) [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: No ]
    Baseline is defined as up to 3 days predose (Week -1)


Enrollment: 36
Study Start Date: December 2011
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Canagliflozin Drug: Canagliflozin
Type = exact number, unit = mg, number = 300, form = capsule, route = oral use. One encapsulated tablet once daily for up to approximately 85 days (approximately 12 weeks)
Placebo Comparator: Placebo Drug: Placebo
Form = capsules, route = oral use. One capsule once daily for up to approximately 85 days (approximately 12 weeks)

Detailed Description:

This is a double-blind (neither the patient or study staff will know the identity of the treatment assigned) in patients with Type 2 Diabetes Mellitus (T2DM) who have inadequate glycemic (blood sugar) control on metformin monotherapy (metformin taken alone for control of T2DM) and who are currently being treated for hypertension (high blood pressure) with agents called angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs). In the study, patients will be randomized (assigned by chance) to receive treatment with canagliflozin or a placebo (a treatment identical in appearance to canagliflozin but does not contain active drug) for 12 weeks. During the 12-week treatment period, patients will also take metformin at a dose of at least 1500 mg/day in addition to their prescribed ACEI or ARB for hypertension. Patients will participate in the study for up to approximately 22 weeks.

  Eligibility

Ages Eligible for Study:   25 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • All patients must have a diagnosis of T2DM with inadequate glycemic control (ie, HbA1c of >=7.0% and <=9.0% at Screening) on metformin monotherapy and be receiving therapy with an antihypertensive agent (an ACEI or ARB) for at least 4 weeks prior to Screening

Exclusion Criteria:

-History of diabetic ketoacidosis, type 1 diabetes mellitus (T1DM), pancreas or beta cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy; or a severe hypoglycemic episode within 6 months before screening

  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: NCT01483781

Locations
Germany
Neuss, Germany
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC L.L.C. Clinical Trial Janssen Research & Development, LLC
  More Information

Additional Information:
No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01483781     History of Changes
Other Study ID Numbers: CR100685, 28431754DIA1047, 2011-004117-17
Study First Received: November 30, 2011
Last Updated: August 19, 2014
Health Authority: Germany: Bundesinstitute fur Arzneimittel and Medizinproduckte (Federal Institute for Medicinal products and Devices)

Keywords provided by Janssen Research & Development, LLC:
Diabetes Mellitus, Type 2
Plasma Volume
Canagliflozin
Metformin
Hemoglobin A1c
Hypertension
Angiotensin-Converting Enzyme Inhibitors (ACEIs)
Angiotensin Receptor Blockers (ARBs)
Pharmacodynamics
Pharmacokinetics
Plasma volume

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 29, 2014