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

Phase 1

Completed

• Conditions: Type 2 Diabetes Mellitus
• Interventions: Drug: ISIS 388626

• Registration Number: NCT00836225
• Lead Sponsor: Ionis Pharmaceuticals, Inc.

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.

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 Timeline

• Study Start: 2009-01
• Study First Submitted: 2009-02-02
• Study First Submitted QC: 2009-02-02
• Study First Posted: 2009-02-04
• Primary Completion: 2011-10
• Study Completion: 2012-01
• Status Verified: 2012-02
• Last Update Submitted: 2012-02-02
• Last Update Posted: 2012-02-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 103

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A	ISIS 388626	50 mg ISIS 388626 vs Placebo, s.c. injection
AAA	ISIS 388626	50 mg ISIS 388626, weekly s.c. injection for 13 weeks vs Placebo
BBB	ISIS 388626	100 mg ISIS 388626, weekly s.c. injection for 13 weeks vs Placebo
CCC	ISIS 388626	200 mg ISIS 388626, weekly s.c. injection for 13 weeks vs Placebo
FFF	ISIS 388626	50 mg ISIS 388626, weekly s.c. injection for 13 weeks vs Placebo
B	ISIS 388626	100 mg ISIS 388626 vs Placebo, s.c. injection
C	ISIS 388626	200 mg ISIS 388626 vs Placebo, s.c. injection
D	ISIS 388626	400 mg ISIS 388626 vs Placebo, s.c. injection
AA	ISIS 388626	50 mg ISIS 388626, 3x over 1 week s.c. injection, weekly s.c. injection for 5 weeks vs Placebo
BB	ISIS 388626	100 mg ISIS 388626, 3x over 1 week s.c. injection, weekly s.c. injection for 5 weeks vs Placebo

Primary Outcome Measures

Name	Time	Method
To evaluate the safety and tolerability of single and multiple doses of ISIS-SGLT2Rx administered subcutaneously	30 days for single dose, 11 weeks for 6-week dosing, 18 weeks for 13-week dosing

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetic profile all doses and Pharmacodynamics for multi-dose groups	3 days for single dose, 11 weeks for 6-week dosing, 18 weeks for 13-week dosing

Trial Locations

Locations (1)

Center for Human Drug Research; 🇳🇱 Leiden, Netherlands