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

Ionis Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: ISIS 388626

Study type: Interventional

Funder types: Industry

Identifiers

NCT00836225

ISIS 388626-CS1

Details and patient eligibility

About

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.

Full 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.

Enrollment: 103 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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103 participants in 10 patient groups

A

Experimental group

Description:

50 mg ISIS 388626 vs Placebo, s.c. injection

Treatment:

Drug: ISIS 388626

B

Experimental group

Description:

100 mg ISIS 388626 vs Placebo, s.c. injection

Treatment:

Drug: ISIS 388626

C

Experimental group

Description:

200 mg ISIS 388626 vs Placebo, s.c. injection

Treatment:

Drug: ISIS 388626

D

Experimental group

Description:

400 mg ISIS 388626 vs Placebo, s.c. injection

Treatment:

Drug: ISIS 388626

AA

Experimental group

Description:

50 mg ISIS 388626, 3x over 1 week s.c. injection, weekly s.c. injection for 5 weeks vs Placebo

Treatment:

Drug: ISIS 388626

BB

Experimental group

Description:

100 mg ISIS 388626, 3x over 1 week s.c. injection, weekly s.c. injection for 5 weeks vs Placebo

Treatment:

Drug: ISIS 388626

AAA

Experimental group

Description:

50 mg ISIS 388626, weekly s.c. injection for 13 weeks vs Placebo

Treatment:

Drug: ISIS 388626

BBB

Experimental group

Description:

100 mg ISIS 388626, weekly s.c. injection for 13 weeks vs Placebo

Treatment:

Drug: ISIS 388626

CCC

Experimental group

Description:

200 mg ISIS 388626, weekly s.c. injection for 13 weeks vs Placebo

Treatment:

Drug: ISIS 388626

FFF

Experimental group

Description:

50 mg ISIS 388626, weekly s.c. injection for 13 weeks vs Placebo

Treatment:

Drug: ISIS 388626