Evaluation of Blood Pressure Reduction, Safety, and Tolerability of Canagliflozin in Patients With Hypertension and Type 2 Diabetes Mellitus on Stable Doses of Anti-hyperglycemic and Anti-hypertensive Agents

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Scientific Affairs, LLC
ClinicalTrials.gov Identifier:
NCT01939496
First received: September 6, 2013
Last updated: March 8, 2016
Last verified: March 2016
  Purpose
The purpose of this study is to evaluate the effect of canagliflozin (JNJ-28431754) on blood pressure reduction, compared to placebo, in patients with hypertension and type 2 diabetes mellitus and who are on stable doses of anti-hyperglycemic and anti-hypertensive agents. Overall safety and tolerability of canagliflozin will be assessed.

Condition Intervention Phase
Diabetes Mellitus, Type 2
Hypertension
Drug: Canagliflozin
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study to Evaluate the Blood Pressure Reduction With Ambulatory Blood Pressure Monitoring (ABPM), Safety, and Tolerability of Canagliflozin in the Treatment of Subjects With Hypertension and Type 2 Diabetes Mellitus

Resource links provided by NLM:


Further study details as provided by Janssen Scientific Affairs, LLC:

Primary Outcome Measures:
  • Change From Baseline in the Mean 24-Hour Systolic Blood Pressure (SBP) to Week 6 [ Time Frame: Baseline and Week 6 ] [ Designated as safety issue: No ]
    The blood pressure (BP) was evaluated by Ambulatory Blood Pressure Monitoring (ABPM) for all participants based on the 24-hour BP recordings.


Secondary Outcome Measures:
  • Change From Baseline in Mean 24-Hour Systolic Blood Pressure (SBP) to Day 2 [ Time Frame: Baseline and Day 2 ] [ Designated as safety issue: No ]
    The blood pressure (BP) was evaluated by Ambulatory Blood Pressure Monitoring (ABPM) for all participants based on the 24-hour BP recordings.

  • Change From Baseline in the Mean 24-Hour Diastolic Blood Pressure (DBP) to Day 2 and to Week 6 [ Time Frame: Baseline, Day 2 and Week 6 ] [ Designated as safety issue: No ]
    The blood pressure (BP) was evaluated by Ambulatory Blood Pressure Monitoring (ABPM) for all participants based on the 24-hour BP recordings.

  • Change From Baseline in Mean Daytime Systolic Blood Pressure (SBP) to Day 2 and to Week 6 [ Time Frame: Baseline, Day 2 and Week 6 ] [ Designated as safety issue: No ]
    The diurnal rise (daytime) in blood pressure (BP) was evaluated by Ambulatory Blood Pressure Monitoring (ABPM) for all participants based on the 24-hour BP recordings.

  • Change From Baseline in Mean Daytime Diastolic Blood Pressure (DBP) to Day 2 and to Week 6 [ Time Frame: Baseline, Day 2 and Week 6 ] [ Designated as safety issue: No ]
    The diurnal rise (daytime) in blood pressure (BP) was evaluated by Ambulatory Blood Pressure Monitoring (ABPM) for all participants based on the 24-hour BP recordings.

  • Change From Baseline in Mean Nighttime Systolic Blood Pressure (SBP) to Day 2 and to Week 6 [ Time Frame: Baseline, Day 2 and Week 6 ] [ Designated as safety issue: No ]
    The nocturnal fall (nighttime) in blood pressure (BP) was evaluated by Ambulatory Blood Pressure Monitoring (ABPM) for all participants based on the 24-hour BP recordings.

  • Change From Baseline in Mean Nighttime Diastolic Blood Pressure (DBP) to Day 2 and to Week 6 [ Time Frame: Baseline, Day 2 and Week 6 ] [ Designated as safety issue: No ]
    The nocturnal fall (nighttime) in blood pressure (BP) was evaluated by Ambulatory Blood Pressure Monitoring (ABPM) for all participants based on the 24-hour BP recordings.

  • Change From Baseline in Fasting Plasma Glucose (FPG) to Week 6 [ Time Frame: Baseline and Week 6 ] [ Designated as safety issue: No ]
    The fasting plasma glucose was evaluated.

  • Change From Baseline in Body Weight to Week 6 [ Time Frame: Baseline and Week 6 ] [ Designated as safety issue: No ]
    Body weight was evaluated.

  • Change From Baseline in Seated Office Blood Pressure (BP) to Day 2, to Week 3, and to Week 6 [ Time Frame: Baseline, Day 2, Week 3 and 6 ] [ Designated as safety issue: No ]
    The seated office blood pressure (BP) was evaluated for all participants based on the 24-hour BP recordings. SBP=Systolic Blood Pressure and DBP=Diastolic Blood Pressure.

  • Change From Baseline in Standing Office Blood Pressure (BP) to Day 2, to Week 3, and to Week 6 [ Time Frame: Baseline, Day 2, Week 3 and 6 ] [ Designated as safety issue: No ]
    The standing office blood pressure (BP) was evaluated for all participants based on the 24-hour BP recordings. SBP=Systolic Blood Pressure and DBP=Diastolic Blood Pressure.

  • Change From Baseline in Seated Heart Rate (HR) to Day 2, to Week 3, and to Week 6 [ Time Frame: Baseline, Day 2, Week 3 and 6 ] [ Designated as safety issue: No ]
    The seated heart rate was evaluated.

  • Change From Baseline in Standing Heart Rate (HR) to Day 2, to Week 3, and to Week 6 [ Time Frame: Baseline, Day 2, Week 3 and 6 ] [ Designated as safety issue: No ]
    The standing heart rate was evaluated.

  • Change From Baseline in the Difference in Seated Office Blood Pressure (BP) and Standing Office BP to Day 2, to Week 3, and to Week 6 [ Time Frame: Baseline, Day 2, Week 3 and 6 ] [ Designated as safety issue: No ]
    The difference in seated office blood pressure and standing office blood pressure was evaluated.

  • Change From Baseline in the Difference in Seated Heart Rate (HR) and Standing HR to Day 2, to Week 3, and to Week 6 [ Time Frame: Baseline, Day 2, Week 3 and 6 ] [ Designated as safety issue: No ]
    The difference in seated heart rate and standing heart rate was evaluated.


Enrollment: 171
Study Start Date: October 2013
Study Completion Date: April 2015
Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Canagliflozin 100 mg
Each patient will receive 100 mg of canagliflozin once daily for 6 weeks.
Drug: Canagliflozin
One 100 mg or 300 mg over-encapsulated tablet orally (by mouth) in addition to the patient's anti-hyperglycemic agents (AHA) regimen used in accordance with local prescribing information.
Experimental: Canagliflozin 300 mg
Each patient will receive 300 mg of canagliflozin once daily for 6 weeks.
Drug: Canagliflozin
One 100 mg or 300 mg over-encapsulated tablet orally (by mouth) in addition to the patient's anti-hyperglycemic agents (AHA) regimen used in accordance with local prescribing information.
Placebo Comparator: Placebo
Each patient will receive matching placebo once daily for 6 weeks.
Drug: Placebo
One matching placebo capsule orally in addition to the patient's anti-hyperglycemic agents (AHA) regimen used in accordance with local prescribing information.

Detailed Description:
This is a randomized (study drug assigned by chance), double blind (neither the patient nor the study doctor will know the name of the assigned treatment), parallel-group, 3-arm (patients will be assigned to 1 of 3 treatment groups) multicenter study to determine the effect of canagliflozin (100 mg and 300 mg) on blood pressure (BP) reduction compared to placebo (a pill that looks like all the other treatments but has no real medicine) in patients with hypertension and type 2 diabetes mellitus (T2DM). The study will consist of 3 phases: a screening phase, a double-blind treatment phase and a follow-up period. Approximately 153 participants will be randomly assigned to 1 of 3 treatment groups (in a 1:1:1 ratio) in the double-blind treatment phase to receive canagliflozin 100 mg, canagliflozin 300 mg or placebo for 6 weeks. The total duration of participation in this study will be approximately 13 weeks.
  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • patients with a diagnosis of type 2 diabetes mellitus
  • patients with hypertension (seated office SBP of >=130 mmHg and <160 mmHg and seated office DBP of >= 70 mmHg at screening and at Week -2
  • patients on stable doses of 1 to 3 anti-hypertensive agents for at least 5 weeks before screening
  • patients on stable doses of 1 to 3 oral anti-hyperglycemic agents which must include metformin, for at least 8 weeks before screening

Exclusion Criteria:

  • a history of diabetic ketoacidosis
  • type 1 diabetes mellitus (T1DM)
  • pancreas or beta-cell transplantation
  • fasting C-peptide <0.70 ng/mL (0.23 nmol/L)
  • body mass index <30 kg/m2
  • has ongoing, inadequately controlled thyroid disorder
  • has a history of cardio-renal disease that required treatment with immunosuppressive therapy.
  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: NCT01939496

  Show 57 Study Locations
Sponsors and Collaborators
Janssen Scientific Affairs, LLC
Investigators
Study Director: Janssen Scientific Affairs, LLC Clinical Trial Janssen Scientific Affairs, LLC
  More Information

Responsible Party: Janssen Scientific Affairs, LLC
ClinicalTrials.gov Identifier: NCT01939496     History of Changes
Other Study ID Numbers: CR102208  28431754DIA4002 
Study First Received: September 6, 2013
Results First Received: March 8, 2016
Last Updated: March 8, 2016
Health Authority: United States: Food and Drug Administration
United States: Federal Government

Keywords provided by Janssen Scientific Affairs, LLC:
Diabetes Mellitus, Type 2
Hypertension
Canagliflozin
JNJ 28431754
Sodium-Glucose Transporter 2
Blood Glucose
Type 2 Diabetes Mellitus

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Hypertension
Cardiovascular Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Vascular Diseases
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 02, 2016