A Study of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS)

This study has been completed.
Sponsor:
Information provided by:
Cytokinetics
ClinicalTrials.gov Identifier:
NCT01089010
First received: March 16, 2010
Last updated: May 11, 2011
Last verified: May 2011

March 16, 2010
May 11, 2011
March 2010
November 2010   (final data collection date for primary outcome measure)
The primary objective of this study is to demonstrate a pharmacodynamic effect of CK-2017357 on measures of skeletal muscle function or fatigability in patients with ALS. [ Time Frame: 2 days ] [ Designated as safety issue: No ]

In this hypothesis-generating early Phase II study, multiple assessments of skeletal muscle function will be made without specifying a single primary endpoint, including:

  1. ALS Functional Assessment
  2. Maximum Grip Strength (bilateral)
  3. Maximum Grip Strength Fatigability (bilateral)
  4. Shoulder Extension Fatigue (bilateral)
  5. Slow Vital Capacity
  6. Maximal Voluntary Ventilation
  7. Sniff Inspiratory Pressure
  8. Maximum Voluntary Muscle Contraction of multiple bilateral muscle groups using Hand Held Dynamometry
  9. Repeated Sub-Maximum Grip Strength Fatigability (bilateral)
Same as current
Complete list of historical versions of study NCT01089010 on ClinicalTrials.gov Archive Site
  • To evaluate and characterize the relationship, if any, between the plasma concentration of CK-2017357 and its pharmacodynamic effects (PK/PD relationship) [ Time Frame: 2 day ] [ Designated as safety issue: No ]
  • To evaluate the safety and tolerability of 2 doses of CK-2017357 given as single doses administered orally to patients with ALS [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
  • To evaluate the effect of CK-2017357 on patient and investigator determined global functional assessment [ Time Frame: 2 days ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
A Study of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS)
A Phase II, Double-Blind, Randomized, Placebo-Controlled, Three-Way Crossover, Pharmacokinetic and Pharmacodynamic Study of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS)

The primary objective of this study is to demonstrate a pharmacodynamic effect of CK 2017357 on measures of skeletal muscle function or fatigability in patients with ALS.

This study is a Phase II, double-blind, randomized, placebo-controlled, three-way crossover study of CK-2017357 in patients with ALS. 36 to 72 patients will be randomized to one of six different treatment sequences. Each treatment sequence consists of three dosing periods; in each dosing period¸ patients receive a single oral dose of placebo, 250 mg of CK-2017357, or 500 mg of CK-2017357. All six treatment sequences will enroll approximately the same number of patients. A washout period of at least 6 days (to a maximum of 10 days) will be employed between the doses for each patient. This study is designed to assess the effect of CK-2017357 on maximal voluntary muscle strength, on the development of fatigue at maximal and sub-maximal voluntary muscle contraction, and on selected pulmonary function parameters. The plasma concentration of CK-2017357 will be measured at selected time points after each of two single doses of CK-2017357 in men and women. The plasma concentration versus time data obtained in this study may be used to develop a population PK model and estimate inter-subject variability of PK parameters in this target patient population, in particular between male and female study patients.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Amyotrophic Lateral Sclerosis
  • Drug: Placebo
    Matching placebo in capsules administered as a single oral dose.
  • Drug: 250 mg CK-2017357
    250 mg CK-2017357 in capsules administered as a single oral dose.
  • Drug: 500 mg CK-2017357
    500 mg CK-2017357 in capsules administered as a single oral dose.
Experimental: Three-way crossover
2 oral dose levels of CK-2017357 and placebo
Interventions:
  • Drug: Placebo
  • Drug: 250 mg CK-2017357
  • Drug: 500 mg CK-2017357
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
67
November 2010
November 2010   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Able to comprehend and willing to sign an Informed Consent Form (ICF)
  • A diagnosis of familial or sporadic ALS (defined as meeting the possible, laboratory-supported probable, probable, or definite criteria for a diagnosis of ALS according to the World Federation of Neurology El Escorial criteria) (Brooks, et al., 2000)
  • Males or Females 18 years of age or older
  • Body mass index (BMI) of 18.0 to 30.0 kg/m2, inclusive
  • Maximum voluntary grip strength between 10 & 40 pounds (females) and 10 & 60 pounds (males)
  • Able to maintain grip contraction for 15 seconds
  • Upright Slow Vital Capacity (SVC) ≥40% of predicted for age, height, and sex
  • Able to perform pulmonary function tests
  • Pre-study clinical laboratory findings (including troponin I (TnI) and CPK) within normal range, or if outside of the normal range, deemed not clinically significant by the Investigator
  • For female patients only: The patient is post-menopausal (≥ 1 year) or sterilized, or if she is of childbearing potential, she is not breastfeeding, her pregnancy test is negative, she has no intention to become pregnant during the course of the study, and she is using contraceptive drugs or devices. For male patients only: Male patients agree for the duration of the study and 10 weeks after the end of the study to use a condom during sexual intercourse with female partners who are of reproductive potential and to have female partners use an additional effective means of contraception (e.g., diaphragm plus spermicide, or oral contraceptives) or the male patient must agree to abstain from sexual intercourse for 10 weeks after the end of the study.

Exclusion Criteria:

  • Significant hepatic/renal insufficiency as defined by Upper Limit of Normal (ULN) laboratory findings
  • Life expectancy <3 months
  • Participation in any trial in which receipt of investigational study drug occurred within 30 days prior to dosing
  • Any prior treatment with CK-2017357
  • In the opinion of the Investigator, the patient is not suitable to participate in the study
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01089010
CY 4021
No
Andrew Wolff, MD, FACC, Chief Medical Officer, Cytokinetics, Inc.
Cytokinetics
Not Provided
Study Chair: Jeremy M Shefner, MD, PhD State University of New York - Upstate Medical University
Cytokinetics
May 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP