Safety Study of ISIS 325568 in Healthy Volunteers

Ionis Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: ISIS 325568

Study type: Interventional

Funder types: Industry

Identifiers

NCT00519727

ISIS 325568-CS1

EudraCT No: 2007-000235-25

Details and patient eligibility

About

The primary purpose of this trial is to assess the safety of ISIS 325568 when given at increasing single doses and to assess the safety of the same doses when given multiple times.

Full description

To evaluate the safety of a single subcutaneous injection of ISIS 325568 administered at four increasing dose levels (50, 100, 200, 400 mg/week) and to evaluate the safety and tolerability of multiple doses of ISIS 325568 (three intravenous doses during Study Week 1, followed by once weekly subcutaneous administration for 5 weeks) at each of the four dose levels

Enrollment: 60 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Age 18 to 65 years
2. Males or females. Females must be non-pregnant and non-lactating, and either surgically sterile (hysterectomy, oophorectomy, or tubal ligation) or post-menopausal. Males must be surgically sterile, abstinent or if engaged in sexual relations of child-bearing potential, subject or partner must be using an acceptable contraceptive method during the trial and for 9 weeks after the last dose of study drug.
3. Give written informed consent to participate in study and availability for all study requirements
4. Fasting plasma glucose ≤ the upper limit of the laboratory's reference range (ULN)
5. HbA1C ≤ ULN
6. BMI < 30 kg/m2

Exclusion criteria

1. Clinically significant abnormalities in medical history or physical examination
2. Abnormalities on laboratory examination (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)
3. History of clinically significant abnormalities in coagulation parameters
4. Positive test result for HIV, hepatitis B virus, and/or hepatitis C virus
5. Active infection requiring antiviral or antimicrobial therapy
6. Subjects on chronic or acute prescription medication may be permitted after discussion with the Isis Medical Monitor.
7. Malignancy (with the exception of basal or squamous cell carcinoma of the skin if adequately treated and no recurrence for > 1 year)
8. Any other concurrent condition which, in the opinion of the Investigator, would preclude participation in this study or interfere with compliance
9. History of alcohol or drug abuse
10. Undergoing or have undergone treatment with another investigational drug, biologic agent or device within 90 days prior to Screening.
11. 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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60 participants in 8 patient groups

A

Experimental group

Description:

50 mg ISIS 325568 vs Placebo, s.c. injection

Treatment:

Drug: ISIS 325568

B

Experimental group

Description:

100 mg ISIS 325568 vs Placebo , s.c. injection

Treatment:

Drug: ISIS 325568

C

Experimental group

Description:

200 mg ISIS 325568 vs Placebo , s.c. injection

Treatment:

Drug: ISIS 325568

D

Experimental group

Description:

400 mg ISIS 325568 vs Placebo, s.c. injection

Treatment:

Drug: ISIS 325568

AA

Experimental group

Description:

50 mg ISIS 325568, 3x over 1 week i.v. infusion, weekly s.c. injection for 5 weeks vs Placebo

Treatment:

Drug: ISIS 325568

BB

Experimental group

Description:

100 mg ISIS 325568, 3x over 1 week i.v. infusion, weekly s.c. injection for 5 weeks vs Placebo

Treatment:

Drug: ISIS 325568

CC

Experimental group

Description:

200 mg ISIS 325568, 3x over 1 week i.v. infusion, weekly s.c. injection for 5 weeks vs Placebo

Treatment:

Drug: ISIS 325568

DD

Experimental group

Description:

400 mg ISIS 325568, 3x over 1 week i.v. infusion, weekly s.c. injection for 5 weeks vs Placebo

Treatment:

Drug: ISIS 325568