Clinical trial NCT00836225: Safety, Tolerability and Activity Study of Multiple Doses of ISIS-SGLT2Rx in Healthy Volunteers
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 2 Diabetes Mellitus
Keywords: diabetes
SGLT2 inhibitor
Lead sponsor: Ionis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2009-02-04
Enrollment: 103
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: To evaluate the safety and tolerability of single and multiple doses of ISIS-SGLT2Rx administered subcutaneously
timeFrame: 30 days for single dose, 11 weeks for 6-week dosing, 18 weeks for 13-week dosing
Secondary outcomes:
measure: Pharmacokinetic profile all doses and Pharmacodynamics for multi-dose groups
timeFrame: 3 days for single dose, 11 weeks for 6-week dosing, 18 weeks for 13-week dosing
Other outcomes:
Locations:
city: Leiden
country: Netherlands
facility: Center for Human Drug Research
Study officials:
affiliation: Center for Human Drug Research
name: Adam Cohen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: