Safety, Tolerability and Activity Study of Multiple Doses of ISIS-SGLT2Rx in Healthy Volunteers

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Isis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00836225
First received: February 2, 2009
Last updated: February 2, 2012
Last verified: February 2012
  Purpose

The primary purpose of this trial is to assess the safety and tolerability of ISIS-SGLT2Rx when given at increasing single doses and to assess the safety and tolerability of the same doses when given multiple times.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: ISIS 388626
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase I , Double-Blind, Placebo-Controlled, Dose-Escalation Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of ISIS 388626 Administered to Healthy Volunteers

Resource links provided by NLM:


Further study details as provided by Isis Pharmaceuticals:

Primary Outcome Measures:
  • To evaluate the safety and tolerability of single and multiple doses of ISIS-SGLT2Rx administered subcutaneously [ Time Frame: 30 days for single dose, 11 weeks for 6-week dosing, 18 weeks for 13-week dosing ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pharmacokinetic profile all doses and Pharmacodynamics for multi-dose groups [ Time Frame: 3 days for single dose, 11 weeks for 6-week dosing, 18 weeks for 13-week dosing ] [ Designated as safety issue: No ]

Enrollment: 103
Study Start Date: January 2009
Study Completion Date: January 2012
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
50 mg ISIS 388626 vs Placebo, s.c. injection
Drug: ISIS 388626

4 arms of single dose s.c. injections: A 50 mg, B 100 mg, C 200 mg, D 400 mg, 2 arms of multi-dose: 3 s.c. injections over 1 week followed by 5 weekly s.c. injections: AA 50 mg, BB 100 mg 3 arms of multi-dose 13 weekly s.c. injections: AAA 50 mg, BBB 100 mg, CCC 200 mg, FFF 50 mg

Placebo: 0.9% sterile saline

Experimental: B
100 mg ISIS 388626 vs Placebo, s.c. injection
Drug: ISIS 388626

4 arms of single dose s.c. injections: A 50 mg, B 100 mg, C 200 mg, D 400 mg, 2 arms of multi-dose: 3 s.c. injections over 1 week followed by 5 weekly s.c. injections: AA 50 mg, BB 100 mg 3 arms of multi-dose 13 weekly s.c. injections: AAA 50 mg, BBB 100 mg, CCC 200 mg, FFF 50 mg

Placebo: 0.9% sterile saline

Experimental: C
200 mg ISIS 388626 vs Placebo, s.c. injection
Drug: ISIS 388626

4 arms of single dose s.c. injections: A 50 mg, B 100 mg, C 200 mg, D 400 mg, 2 arms of multi-dose: 3 s.c. injections over 1 week followed by 5 weekly s.c. injections: AA 50 mg, BB 100 mg 3 arms of multi-dose 13 weekly s.c. injections: AAA 50 mg, BBB 100 mg, CCC 200 mg, FFF 50 mg

Placebo: 0.9% sterile saline

Experimental: D
400 mg ISIS 388626 vs Placebo, s.c. injection
Drug: ISIS 388626

4 arms of single dose s.c. injections: A 50 mg, B 100 mg, C 200 mg, D 400 mg, 2 arms of multi-dose: 3 s.c. injections over 1 week followed by 5 weekly s.c. injections: AA 50 mg, BB 100 mg 3 arms of multi-dose 13 weekly s.c. injections: AAA 50 mg, BBB 100 mg, CCC 200 mg, FFF 50 mg

Placebo: 0.9% sterile saline

Experimental: AA
50 mg ISIS 388626, 3x over 1 week s.c. injection, weekly s.c. injection for 5 weeks vs Placebo
Drug: ISIS 388626

4 arms of single dose s.c. injections: A 50 mg, B 100 mg, C 200 mg, D 400 mg, 2 arms of multi-dose: 3 s.c. injections over 1 week followed by 5 weekly s.c. injections: AA 50 mg, BB 100 mg 3 arms of multi-dose 13 weekly s.c. injections: AAA 50 mg, BBB 100 mg, CCC 200 mg, FFF 50 mg

Placebo: 0.9% sterile saline

Experimental: BB
100 mg ISIS 388626, 3x over 1 week s.c. injection, weekly s.c. injection for 5 weeks vs Placebo
Drug: ISIS 388626

4 arms of single dose s.c. injections: A 50 mg, B 100 mg, C 200 mg, D 400 mg, 2 arms of multi-dose: 3 s.c. injections over 1 week followed by 5 weekly s.c. injections: AA 50 mg, BB 100 mg 3 arms of multi-dose 13 weekly s.c. injections: AAA 50 mg, BBB 100 mg, CCC 200 mg, FFF 50 mg

Placebo: 0.9% sterile saline

Experimental: AAA
50 mg ISIS 388626, weekly s.c. injection for 13 weeks vs Placebo
Drug: ISIS 388626

4 arms of single dose s.c. injections: A 50 mg, B 100 mg, C 200 mg, D 400 mg, 2 arms of multi-dose: 3 s.c. injections over 1 week followed by 5 weekly s.c. injections: AA 50 mg, BB 100 mg 3 arms of multi-dose 13 weekly s.c. injections: AAA 50 mg, BBB 100 mg, CCC 200 mg, FFF 50 mg

Placebo: 0.9% sterile saline

Experimental: BBB
100 mg ISIS 388626, weekly s.c. injection for 13 weeks vs Placebo
Drug: ISIS 388626

4 arms of single dose s.c. injections: A 50 mg, B 100 mg, C 200 mg, D 400 mg, 2 arms of multi-dose: 3 s.c. injections over 1 week followed by 5 weekly s.c. injections: AA 50 mg, BB 100 mg 3 arms of multi-dose 13 weekly s.c. injections: AAA 50 mg, BBB 100 mg, CCC 200 mg, FFF 50 mg

Placebo: 0.9% sterile saline

Experimental: CCC
200 mg ISIS 388626, weekly s.c. injection for 13 weeks vs Placebo
Drug: ISIS 388626

4 arms of single dose s.c. injections: A 50 mg, B 100 mg, C 200 mg, D 400 mg, 2 arms of multi-dose: 3 s.c. injections over 1 week followed by 5 weekly s.c. injections: AA 50 mg, BB 100 mg 3 arms of multi-dose 13 weekly s.c. injections: AAA 50 mg, BBB 100 mg, CCC 200 mg, FFF 50 mg

Placebo: 0.9% sterile saline

Experimental: FFF
50 mg ISIS 388626, weekly s.c. injection for 13 weeks vs Placebo
Drug: ISIS 388626

4 arms of single dose s.c. injections: A 50 mg, B 100 mg, C 200 mg, D 400 mg, 2 arms of multi-dose: 3 s.c. injections over 1 week followed by 5 weekly s.c. injections: AA 50 mg, BB 100 mg 3 arms of multi-dose 13 weekly s.c. injections: AAA 50 mg, BBB 100 mg, CCC 200 mg, FFF 50 mg

Placebo: 0.9% sterile saline


Detailed Description:

To evaluate the safety and tolerability of a single subcutaneous injection of ISIS-SGLT2Rx administered at four increasing dose levels (50, 100, 200, 400 mg) and to evaluate the safety and tolerability of multiple doses of ISIS 388626 administered subcutaneously of either 6 or 13 weeks.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Age 18 to 65 years
  • Male or female gender although females must be post-menopausal or surgically sterile (hysterectomy, oophorectomy or tubal ligation)
  • Give written informed consent to participate in the study and availability for all study requirements
  • Fasting plasma glucose </= the upper limit of the laboratory's reference range (ULN)
  • HbA1c </= ULN
  • BMI < 30 kg/m²
  • Agree to maintain steady hydration throughout study participation and agree not to fluid restrict

Exclusion Criteria:

  • Pregnant women, nursing mothers or women of childbearing potential
  • Clinically significant abnormalities in medical history or physical examination
  • Clinically significant abnormalities in laboratory examination (including ALT > ULN, AST > ULN, bilirubin > ULN, creatinine > ULN, urine protein positive by urine dipstick, platelets < lower limit of normal and any other clinically significant laboratory findings)
  • Estimated GFR < 60 mL/min per 1.73m²
  • History of clinically significant abnormalities in coagulation parameters
  • Positive test result for HIV, hepatitis B virus, and/or hepatitis C virus
  • Active infection requiring antiviral or antimicrobial therapy
  • Subjects on chronic or acute prescription medication may be permitted after discussion with the Isis Medical Monitor
  • Malignancy (with the exception of basal or squamous cell carcinoma of the skin if adequately treated and no recurrence for > 1 year)
  • Any other concurrent condition which, in the opinion of the Investigator, would preclude participation in this study or interfere with compliance
  • Past and present history of alcohol or drug abuse (defined as > 3 units daily)
  • Undergoing or have undergone treatment with another investigational drug, biologic agent or device within 90 days prior to Screening
  • Blood donation within three months of Screening
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00836225

Locations
Netherlands
Center for Human Drug Research
Leiden, Netherlands
Sponsors and Collaborators
Isis Pharmaceuticals
Investigators
Principal Investigator: Adam Cohen, MD, PhD Center for Human Drug Research
  More Information

No publications provided

Responsible Party: Isis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00836225     History of Changes
Other Study ID Numbers: ISIS 388626-CS1
Study First Received: February 2, 2009
Last Updated: February 2, 2012
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Netherlands: Ministry of Health, Welfare and Sport

Keywords provided by Isis Pharmaceuticals:
diabetes
SGLT2 inhibitor

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

ClinicalTrials.gov processed this record on April 15, 2014