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
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: 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 September 18, 2014