A Multiple-Dose, Open-Label, Phase 1, Pharmacokinetic, Pharmacodynamic, and Safety Study of Avonex® in Chinese Healthy Volunteer Subjects

This study has been completed.
Sponsor:
Information provided by:
Biogen Idec
ClinicalTrials.gov Identifier:
NCT01416207
First received: June 30, 2011
Last updated: November 3, 2011
Last verified: November 2011
  Purpose

Rationale for the Study:

The purpose of this study is to characterize the pharmacokinetic (PK) and pharmacodynamic (PD) profile of Avonex in Chinese healthy volunteer subjects. Data from this study will be used to support registration of Avonex in China.

Study Design:

This is a multiple-dose, single-arm, open-label, PK/PD and safety study. Four weekly injections of Avonex will be administered intramuscularly (IM). Frequent (intensive) blood samples will be collected with the first and fourth injections of Avonex, and a sparse blood sample will be collected with the second and third injections of Avonex.


Condition Intervention Phase
Healthy
Drug: Avonex
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: A Multiple-Dose, Open-Label, Phase 1, Pharmacokinetic, Pharmacodynamic, and Safety Study of Avonex® in Chinese Healthy Volunteer Subjects

Resource links provided by NLM:


Further study details as provided by Biogen Idec:

Primary Outcome Measures:
  • Cmax [ Time Frame: Participants will be followed for the duration of the study; and expected 2 months ] [ Designated as safety issue: No ]
  • Tmax [ Time Frame: Participants will be followed for the duration of the study; and expected 2 months ] [ Designated as safety issue: No ]
  • AUC 0-t [ Time Frame: Participants will be followed for the duration of the study; and expected 2 months ] [ Designated as safety issue: No ]
  • AUC 0-infinity [ Time Frame: Participants will be followed for the duration of the study; and expected 2 months ] [ Designated as safety issue: No ]
  • T 1/2 [ Time Frame: Participants will be followed for the duration of the study; and expected 2 months ] [ Designated as safety issue: No ]
  • Tlag [ Time Frame: Participants will be followed for the duration of the study; and expected 2 months ] [ Designated as safety issue: No ]
  • Ka [ Time Frame: Participants will be followed for the duration of the study; and expected 2 months ] [ Designated as safety issue: No ]
  • T 1/2ab [ Time Frame: Participants will be followed for the duration of the study; and expected 2 months ] [ Designated as safety issue: No ]
  • Kcl [ Time Frame: Participants will be followed for the duration of the study; and expected 2 months ] [ Designated as safety issue: No ]
  • Kir [ Time Frame: Participants will be followed for the duration of the study; and expected 2 months ] [ Designated as safety issue: No ]
  • Emax [ Time Frame: Participants will be followed for the duration of the study; and expected 2 months ] [ Designated as safety issue: No ]
  • Tmax(E) [ Time Frame: Participants will be followed for the duration of the study; and expected 2 months ] [ Designated as safety issue: No ]
  • Eauc [ Time Frame: Participants will be followed for the duration of the study; and expected 2 months ] [ Designated as safety issue: No ]
  • Induction ratio [ Time Frame: Participants will be followed for the duration of the study; and expected 2 months ] [ Designated as safety issue: No ]
  • T1/2 return to baseline [ Time Frame: Participants will be followed for the duration of the study; and expected 2 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of Adverse Events as a measure of safety and tolerability [ Time Frame: Participants will be followed for the duration of the study; and expected 2 months ] [ Designated as safety issue: Yes ]
  • Number of Serious Adverse Events as a measure of safety and tolerability [ Time Frame: Participants will be followed for the duration of the study; and expected 2 months ] [ Designated as safety issue: Yes ]
  • Changes in lab assessments [ Time Frame: Participants will be followed for the duration of the study; and expected 2 months ] [ Designated as safety issue: Yes ]
  • Changes in vital signs [ Time Frame: Participants will be followed for the duration of the study; and expected 2 months ] [ Designated as safety issue: Yes ]
  • Changes in physical examinations [ Time Frame: Participants will be followed for the duration of the study; and expected 2 months ] [ Designated as safety issue: Yes ]
  • Changes in ECGs [ Time Frame: Participants will be followed for the duration of the study; and expected 2 months ] [ Designated as safety issue: Yes ]

Enrollment: 24
Study Start Date: August 2011
Study Completion Date: October 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Avonex
4 weekly injections of Avonex (IM)
Drug: Avonex
4 weekly injections of Avonex (IM)
Other Name: Interferon-β1a

Detailed Description:

Rationale for the Study:

The purpose of this study is to characterize the pharmacokinetic (PK) and pharmacodynamic (PD) profile of Avonex in Chinese healthy volunteer subjects. Data from this study will be used to support registration of Avonex in China.

Study Design:

This is a multiple-dose, single-arm, open-label, PK/PD and safety study. Four weekly injections of Avonex will be administered intramuscularly (IM). Frequent (intensive) blood samples will be collected with the first and fourth injections of Avonex, and a sparse blood sample will be collected with the second and third injections of Avonex.

Four Avonex IM injections will be administered in this study. Due to the long-term use of Avonex by MS patients, a multiple-dose PK/PD study is necessary in order to provide adequate information to evaluate changes in drug concentrations over time in Chinese healthy subjects. Serum levels of interferon beta in Caucasian healthy volunteers have been shown to peak between 3 and 15 hours after administration of Avonex IM at the dose being used in this study and have been shown to decline at a rate consistent with a 10-hour elimination half-life; therefore, accumulation of interferon beta following multiple weekly Avonex IM injections is not anticipated.

Exposure of healthy subjects to multiple doses of Avonex in this study is not anticipated to present safety or tolerability issues based on experience from previous Avonex studies that have been conducted in healthy volunteer subjects and MS patients. Flu-like symptoms associated with this dose of Avonex have generally been mostly of mild-to-moderate intensity and of short duration, typically experienced within the first 24 hours after injection. Prophylactic analgesic medication must be administered prior to each Avonex injection during the study which is a recommended practice with the use of interferon therapies in order to ameliorate flu-like symptoms.

Study Location:

China, at 1 Phase 1 study site.

Duration of Treatment and Follow-up:

Approximately 2 months, including a 28-day Screening and Baseline period, a 3-week Treatment and blood sampling period and a 14-day Follow-Up period.

Statistical Methods:

PK/PD parameters will be calculated using non-compartmental methods. Summary statistics for each PK/PD parameter will be calculated. Mean concentration values will be plotted over time both on a linear and a logarithmic scale.

The incidence of treatment-emergent AEs will be summarized. Vital signs will be examined to determine the incidence of clinically relevant abnormalities.

Laboratory evaluations will be assessed to determine the incidence of abnormalities. Changes in laboratory evaluations will be summarized using shift tables and summary statistics.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations.
  • Subjects of Chinese origin (at least both maternal and paternal grandparents of Chinese origin).
  • Body mass index (BMI) within the range of 18.5 to 30 kg/m2 (inclusive).
  • All male subjects and female subjects of childbearing potential must practice effective contraception during the study and be willing and able to continue contraception for 30 days after their last dose of study treatment.

Exclusion Criteria:

  • History of seizure disorder or unexplained blackouts OR history of a seizure within 6 months prior to Day 1.
  • History of suicidal ideation or an episode of clinically severe depression (as determined by the Investigator) within 6 months prior to Day 1.
  • Any clinically significant presence (as determined by the Investigator) of cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, or other major disease.
  • Positive test result for hepatitis C antibody (HCV Ab), or current hepatitis B infection at Screening.
  • Known history of human immunodeficiency virus (HIV).
  • Clinically significant abnormal laboratory values.
  • History of alcohol abuse (as defined by the Investigator), or a positive blood screen test for presence for alcohol at Screening.
  • History of drug abuse (as defined by the Investigator), or a positive urinary screen test for presence of cocaine and morphine.
  • Premalignant and malignant disease.
  • History of clinically significant severe allergic or anaphylactic reactions.
  • Known allergy to any component of the Avonex formulation.
  • History of hypersensitivity or intolerance to prophylactic analgesic medication that would preclude use during the study.
  • Clinically significant abnormal electrocardiogram (ECG) values as determined by the Investigator.
  • Known allergy to interferon beta-1a.
  • Active bacterial or viral infection.
  • Female subjects who are pregnant or currently breastfeeding.
  • Previous participation in another investigational drug study within the last 1 month or 7 half-lives, whichever is longer, or previous participation in this study.
  • Treatment with any prescription medication within 14 days of Day 1.
  • Treatment with any over-the-counter products within the 14 days prior to Day 1.
  • Donation of blood (500 mL or greater) within 56 days prior to Day 1.
  • Inability to comply with study requirements
  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: NCT01416207

Locations
China
Research Site
Shanghai, China
Sponsors and Collaborators
Biogen Idec
  More Information

No publications provided

Responsible Party: Biogen Idec Limited
ClinicalTrials.gov Identifier: NCT01416207     History of Changes
Other Study ID Numbers: 108HV105
Study First Received: June 30, 2011
Last Updated: November 3, 2011
Health Authority: China: Food and Drug Administration

Additional relevant MeSH terms:
Interferon beta 1a
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 29, 2014