A Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Single Doses of Mipomersen in Japanese Healthy Volunteers

This study has been completed.
Sponsor:
Collaborator:
Isis Pharmaceuticals
Information provided by (Responsible Party):
Genzyme, a Sanofi Company
ClinicalTrials.gov Identifier:
NCT01299298
First received: February 9, 2011
Last updated: April 13, 2012
Last verified: April 2012
  Purpose

This Phase 1 study is being conducted to evaluate 3 increasing subcutaneous (SC) doses (50, mg, 100 mg or 200mg) of mipomersen in Japanese healthy volunteers. Eligible subjects will receive a single study injection of either mipomersen or placebo. Subjects will be enrolled into 1 of 3 treatment cohorts (Cohorts A, B, and C) in a dose-escalation design. Dose-escalation will proceed only if there is an acceptable safety profile from the previous dosing level.


Condition Intervention Phase
Healthy Volunteer
Drug: mipomersen
Drug: placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Prospective, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation, Phase 1 Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Single Doses of Mipomersen Administered Subcutaneously to Japanese Healthy Subjects

Resource links provided by NLM:


Further study details as provided by Genzyme, a Sanofi Company:

Primary Outcome Measures:
  • Maximum plasma concentration (Cmax) [ Time Frame: Baseline up to Day 36 Post-Treatment ] [ Designated as safety issue: No ]
    plasma PK parameters

  • Time to maximal concentration (Tmax) [ Time Frame: Baseline up to Day 36 Post-Treatment ] [ Designated as safety issue: No ]
    plasma PK parameters

  • Area Under the Curve (AUC) [ Time Frame: Baseline up to Day 36 Post-Treatment ] [ Designated as safety issue: No ]
    plasma PK parameters


Secondary Outcome Measures:
  • Number of Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to Day 36 Post-Treatment ] [ Designated as safety issue: Yes ]

Enrollment: 20
Study Start Date: January 2011
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: mipomersen
50 mg (cohort A), 100mg (cohort B) or 200mg (cohort C) SC single dose
Drug: mipomersen
50 mg (cohort A), 100mg (cohort B) or 200mg (cohort C) subcutaneous (SC) single dose of study drug
Other Name: ISIS 301012
Placebo Comparator: placebo
50 mg (cohort A), 100mg (cohort B) or 200mg (cohort C) SC single dose
Drug: placebo
50 mg (cohort A), 100mg (cohort B), or 200mg (cohort C) subcutaneous (SC) single dose of study drug

  Eligibility

Ages Eligible for Study:   20 Years to 45 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • First generation Japanese (born in Japan of Japanese parents and Japanese grandparents), lived no more than 5 years outside of Japan, with no significant change in lifestyle or habits, including diet, while living outside of Japan.
  • Surgically sterile, abstinent or subject or partner compliant with acceptable contraceptive during and 24 weeks after the last study drug dose
  • Body weight >50 kg and body mass index between 18 and 30 kg/m2 inclusive

Exclusion Criteria:

  • Clinically significant cardiovascular, pulmonary, hepatic, renal, haematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, infectious, or psychiatric disease
  • Clinically significant abnormal findings on the physical examination, ECG, blood pressure, heart rate, medical history, or clinical laboratory results at Screening or before dosing
  • Positive test for human immunodeficiency virus (HIV), hepatitis B or C.
  • High sensitivity C-reactive protein (hsCRP) >5 mg/L
  • History of or current malignancy (with the exception of basal or squamous cell carcinoma of the skin if adequately treated and no recurrence for > 1 year)
  • Evidence of acute or ongoing chronic inflammatory condition or infection
  • History of rash, impetigo, or drug allergies
  • Alcohol and/or drug abuse
  • Smoking more than 10 cigarettes per day
  • Planned dental work up to and including Day 8 procedures
  • Treatment with another investigational drug, biological agent, or device within 4 weeks of Screening or 5 half-lives of the study agent, whichever is longer
  • Use of prescribed medications within 4 weeks or over-the counter medications (including dietary supplements and herbal remedies) within 14 days before the first study drug dose, or use of any concomitant medications (prescribed or over the counter) through Day 8 of the study without Investigator and Sponsor approval. Vaccinations are not allowed beginning 3 weeks prior to the first dose of study drug until completion of the safety follow-up period
  • Previous exposure to oligonucleotide-based drug therapy
  • Donated 50 to 499 mL of blood within 30 days prior to consent, or >499 mL within 60 days
  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: NCT01299298

Locations
Germany
FOCUS Clinical Drug Development GmbH
Stresemannallee 6, Neuss, Germany, 41460
Sponsors and Collaborators
Genzyme, a Sanofi Company
Isis Pharmaceuticals
Investigators
Study Director: Medical Monitor Genzyme, a Sanofi Company
  More Information

No publications provided

Responsible Party: Genzyme, a Sanofi Company
ClinicalTrials.gov Identifier: NCT01299298     History of Changes
Other Study ID Numbers: MIPO3700710, 2010-021948-18
Study First Received: February 9, 2011
Last Updated: April 13, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Mipomersen
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Molecular Probes
Diagnostic Uses of Chemicals

ClinicalTrials.gov processed this record on August 25, 2014