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

Type 2 Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00836225
• Other study ID #: ISIS 388626-CS1
• Status: Completed
• Phase: Phase 1
• First received: February 2, 2009
• Last updated: February 2, 2012
• Start date: January 2009
• Est. completion date: January 2012

Study information

• Verified date: February 2012
• Source: Ionis Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)Netherlands: Ministry of Health, Welfare and Sport
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 103
• Est. completion date: January 2012
• Est. primary completion date: October 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

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

Locations

Country	Name	City	State
Netherlands	Center for Human Drug Research	Leiden

Sponsors (1)

Lead Sponsor	Collaborator
Ionis Pharmaceuticals, Inc.

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No