Safety Study of ISIS 325568 in Healthy Volunteers

This study has been completed.
Sponsor:
Information provided by:
Isis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00519727
First received: August 21, 2007
Last updated: August 15, 2008
Last verified: August 2008
  Purpose

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.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: ISIS 325568
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Isis Pharmaceuticals:

Primary Outcome Measures:
  • safety and tolerability [ Time Frame: 30 days for single dose, 16 weeks for multi-dose ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetic profile all doses and Pharmacodynamics for multi-dose groups. [ Time Frame: 4 days for single dose, 16 weeks for multi-dose ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: August 2007
Study Completion Date: June 2008
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
50 mg ISIS 325568 vs Placebo, s.c. injection
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

Experimental: B
100 mg ISIS 325568 vs Placebo , s.c. injection
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

Experimental: C
200 mg ISIS 325568 vs Placebo , s.c. injection
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

Experimental: D
400 mg ISIS 325568 vs Placebo, s.c. injection
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

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

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

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

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


Detailed 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

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00519727

Locations
Netherlands
Centre for Human Drug Research
Leiden, Netherlands
Sponsors and Collaborators
Isis Pharmaceuticals
Investigators
Principal Investigator: J. Burggraaf, MD PhD Centre for Human Drug Research
  More Information

No publications provided

Responsible Party: Sanjay Bhanot, MD, VP of Research and Development, ISIS Pharmaceuticals Medical Monitor
ClinicalTrials.gov Identifier: NCT00519727     History of Changes
Other Study ID Numbers: ISIS 325568-CS1, EudraCT No: 2007-000235-25
Study First Received: August 21, 2007
Last Updated: August 15, 2008
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Isis Pharmaceuticals:
diabetes

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on September 18, 2014