Safety Study of ISIS 325568 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 325568 Administered to Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00519727
• Other study ID #: ISIS 325568-CS1
• Secondary ID: EudraCT No: 2007
• Status: Completed
• Phase: Phase 1
• First received: August 21, 2007
• Last updated: August 15, 2008
• Start date: August 2007
• Est. completion date: June 2008

Study information

• Verified date: August 2008
• Source: Ionis Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: June 2008
• Est. primary completion date: April 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics 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 325568
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

Locations

Country	Name	City	State
Netherlands	Centre 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	safety and tolerability		30 days for single dose, 16 weeks for multi-dose	Yes
Secondary	Pharmacokinetic profile all doses and Pharmacodynamics for multi-dose groups.		4 days for single dose, 16 weeks for multi-dose	No