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

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ClinicalTrials.gov Identifier: NCT00836225
Recruitment Status : Completed
First Posted : February 4, 2009
Last Update Posted : February 3, 2012
Sponsor:
Information provided by (Responsible Party):
Ionis Pharmaceuticals, Inc.

Study Description
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Brief Summary:
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 or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus Drug: ISIS 388626 Phase 1

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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 103 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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
Study Start Date : January 2009
Actual Primary Completion Date : October 2011
Actual Study Completion Date : January 2012

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
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


Outcome Measures
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Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. 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 ]

Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00836225


Locations
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Netherlands
Center for Human Drug Research
Leiden, Netherlands
Sponsors and Collaborators
Ionis Pharmaceuticals, Inc.
Investigators
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Principal Investigator: Adam Cohen, MD, PhD Center for Human Drug Research
More Information
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Responsible Party: Ionis Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT00836225    
Other Study ID Numbers: ISIS 388626-CS1
First Posted: February 4, 2009    Key Record Dates
Last Update Posted: February 3, 2012
Last Verified: February 2012
Keywords provided by Ionis Pharmaceuticals, Inc.:
diabetes
SGLT2 inhibitor
Additional relevant MeSH terms:
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Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases