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

Healthy Volunteer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01299298
• Other study ID #: MIPO3700710
• Secondary ID: 2010-021948-18
• Status: Completed
• Phase: Phase 1
• First received: February 9, 2011
• Last updated: August 1, 2016
• Start date: January 2011
• Est. completion date: April 2011

Study information

• Verified date: August 2016
• Source: Kastle Therapeutics, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: April 2011
• Est. primary completion date: April 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 45 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Healthy Volunteer

Intervention

Drug:
• mipomersen
50 mg (cohort A), 100mg (cohort B) or 200mg (cohort C) subcutaneous (SC) single dose of study drug
• placebo
50 mg (cohort A), 100mg (cohort B), or 200mg (cohort C) subcutaneous (SC) single dose of study drug

Locations

Country	Name	City	State
Germany	FOCUS Clinical Drug Development GmbH	Stresemannallee 6, Neuss

Sponsors (2)

Lead Sponsor	Collaborator
Kastle Therapeutics, LLC	Ionis Pharmaceuticals, Inc.

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum plasma concentration (Cmax)	plasma PK parameters	Baseline up to Day 36 Post-Treatment	No
Primary	Time to maximal concentration (Tmax)	plasma PK parameters	Baseline up to Day 36 Post-Treatment	No
Primary	Area Under the Curve (AUC)	plasma PK parameters	Baseline up to Day 36 Post-Treatment	No
Secondary	Number of Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)		Up to Day 36 Post-Treatment	Yes