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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Drug: mipomersen; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Stresemannallee 6, Neuss, Germany, 41460
    • FOCUS Clinical Drug Development GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum plasma concentration (Cmax)	plasma PK parameters	Baseline up to Day 36 Post-Treatment
Time to maximal concentration (Tmax)	plasma PK parameters	Baseline up to Day 36 Post-Treatment
Area Under the Curve (AUC)	plasma PK parameters	Baseline up to Day 36 Post-Treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	Up to Day 36 Post-Treatment

Collaborators and Investigators

• Sponsor: Kastle Therapeutics, LLC
• Collaborators: Ionis Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): April 1, 2011
• Study Completion (Actual): April 1, 2011

Study Registration Dates

• First Submitted: February 9, 2011
• First Submitted That Met QC Criteria: February 17, 2011
• First Posted (Estimate): February 18, 2011

Study Record Updates

• Last Update Posted (Estimate): August 3, 2016
• Last Update Submitted That Met QC Criteria: August 1, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Mipomersen
• Other Study ID Numbers: MIPO3700710; 2010-021948-18 (EudraCT Number)