Safety Study of ISIS 325568 in Healthy Volunteers

Study Overview
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Brief Summary
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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.

Detailed Description
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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

Official Title
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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 325568 Administered to Healthy Volunteers

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: ISIS 325568


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 to 65 years 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. Give written informed consent to participate in 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 Exclusion Criteria: Clinically significant abnormalities in medical history or physical examination 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) 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 History of alcohol or drug abuse 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>50 mg ISIS 325568 vs Placebo, s.c. injection | Drug: ISIS 325568<br>* 4 arms of single dose s.c. injections: A 50 mg B 100 mg C 200 mg D 400 mg 4 arms of multi-dose: 3 i.v. infusions over 1 week followed by 5 weekly s.c. injections AA 50 mg BB 100 mg CC 200 mg DD 400 mg or EE 50 mg Placebo: 0.9% Sodium Chloride<br>|
| Experimental: B<br>100 mg ISIS 325568 vs Placebo , s.c. injection | Drug: ISIS 325568<br>* 4 arms of single dose s.c. injections: A 50 mg B 100 mg C 200 mg D 400 mg 4 arms of multi-dose: 3 i.v. infusions over 1 week followed by 5 weekly s.c. injections AA 50 mg BB 100 mg CC 200 mg DD 400 mg or EE 50 mg Placebo: 0.9% Sodium Chloride<br>|
| Experimental: C<br>200 mg ISIS 325568 vs Placebo , s.c. injection | Drug: ISIS 325568<br>* 4 arms of single dose s.c. injections: A 50 mg B 100 mg C 200 mg D 400 mg 4 arms of multi-dose: 3 i.v. infusions over 1 week followed by 5 weekly s.c. injections AA 50 mg BB 100 mg CC 200 mg DD 400 mg or EE 50 mg Placebo: 0.9% Sodium Chloride<br>|
| Experimental: D<br>400 mg ISIS 325568 vs Placebo, s.c. injection | Drug: ISIS 325568<br>* 4 arms of single dose s.c. injections: A 50 mg B 100 mg C 200 mg D 400 mg 4 arms of multi-dose: 3 i.v. infusions over 1 week followed by 5 weekly s.c. injections AA 50 mg BB 100 mg CC 200 mg DD 400 mg or EE 50 mg Placebo: 0.9% Sodium Chloride<br>|
| Experimental: AA<br>50 mg ISIS 325568, 3x over 1 week i.v. infusion, weekly s.c. injection for 5 weeks vs Placebo | Drug: ISIS 325568<br>* 4 arms of single dose s.c. injections: A 50 mg B 100 mg C 200 mg D 400 mg 4 arms of multi-dose: 3 i.v. infusions over 1 week followed by 5 weekly s.c. injections AA 50 mg BB 100 mg CC 200 mg DD 400 mg or EE 50 mg Placebo: 0.9% Sodium Chloride<br>|
| Experimental: BB<br>100 mg ISIS 325568, 3x over 1 week i.v. infusion, weekly s.c. injection for 5 weeks vs Placebo | Drug: ISIS 325568<br>* 4 arms of single dose s.c. injections: A 50 mg B 100 mg C 200 mg D 400 mg 4 arms of multi-dose: 3 i.v. infusions over 1 week followed by 5 weekly s.c. injections AA 50 mg BB 100 mg CC 200 mg DD 400 mg or EE 50 mg Placebo: 0.9% Sodium Chloride<br>|
| Experimental: CC<br>200 mg ISIS 325568, 3x over 1 week i.v. infusion, weekly s.c. injection for 5 weeks vs Placebo | Drug: ISIS 325568<br>* 4 arms of single dose s.c. injections: A 50 mg B 100 mg C 200 mg D 400 mg 4 arms of multi-dose: 3 i.v. infusions over 1 week followed by 5 weekly s.c. injections AA 50 mg BB 100 mg CC 200 mg DD 400 mg or EE 50 mg Placebo: 0.9% Sodium Chloride<br>|
| Experimental: DD<br>400 mg ISIS 325568, 3x over 1 week i.v. infusion, weekly s.c. injection for 5 weeks vs Placebo | Drug: ISIS 325568<br>* 4 arms of single dose s.c. injections: A 50 mg B 100 mg C 200 mg D 400 mg 4 arms of multi-dose: 3 i.v. infusions over 1 week followed by 5 weekly s.c. injections AA 50 mg BB 100 mg CC 200 mg DD 400 mg or EE 50 mg Placebo: 0.9% Sodium Chloride<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety and tolerability |  | 30 days for single dose, 16 weeks for multi-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic profile all doses and Pharmacodynamics for multi-dose groups. |  | 4 days for single dose, 16 weeks for multi-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes