A Study of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS)
2019年5月7日 更新者：Cytokinetics
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.
調査の概要
詳細な説明
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.
研究の種類
介入
入学 (実際)
67
段階
- フェーズ2
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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Arizona
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Phoenix、Arizona、アメリカ、85018
- Phoenix Neurological Associates, Ltd.
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California
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Fresno、California、アメリカ、93701
- University Neurology Associates
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San Francisco、California、アメリカ、94115
- California Pacific Medical Center
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Florida
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Jacksonville、Florida、アメリカ、32224
- Mayo Clinic Florida
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Kentucky
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Lexington、Kentucky、アメリカ、40536
- University Of Kentucky
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Maryland
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Baltimore、Maryland、アメリカ、21287
- Johns Hopkins Hospital
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Massachusetts
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Boston、Massachusetts、アメリカ、02114
- Massachusetts General Hospital
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Missouri
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Saint Louis、Missouri、アメリカ、63110
- Washington University
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New York
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Syracuse、New York、アメリカ、13210
- SUNY Upstate Medical Center
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North Carolina
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Durham、North Carolina、アメリカ、27705
- Duke University
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Oregon
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Portland、Oregon、アメリカ、97213
- Providence ALS Center
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Pennsylvania
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Philadelphia、Pennsylvania、アメリカ、19102
- Drexel University College of Medicine, Dept of Neurology
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University Park、Pennsylvania、アメリカ、17033
- Penn State
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Texas
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San Antonio、Texas、アメリカ、78229
- The University of Texas Health Science Center at San Antonio
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Vermont
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Burlington、Vermont、アメリカ、05401
- University of Vermont
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年歳以上 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
Inclusion Criteria
For enrollment, patients were required to satisfy all of the following criteria at baseline:
1. 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, Miller 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 in at least one hand between 10 and 40 pounds (females) or 10 and 60 pounds (males)
- Able to swallow capsules with water
- Upright Slow Vital Capacity (SVC) > 40% of predicted for age, height, and sex [See Appendix 16.6.1]
- Able to perform pulmonary function tests
- Pre-study clinical laboratory findings (including troponin I [TnI] and creatine phosphokinase [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 the duration of the study and for 10 weeks after the end of the study.
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
Patients satisfying any of the following criteria at baseline were excluded from enrollment:
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 times the upper limit of normal (ULN)
- 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
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：クロスオーバー割り当て
- マスキング：4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：Treatment Sequence 1
Treatment sequence 1 consisted of three dosing periods in which patients received single oral doses of placebo, 250 mg, and 500 mg of CK-2017357, in that order, with approximately one week between each dose.
Each patient acted as their own control, as all doses were represented in each treatment sequence.
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単回経口投与として投与されるカプセル中の対応するプラセボ。
単回経口投与として投与されるカプセル中の 250 mg CK-2017357。
他の名前：
500 mg CK-2017357 のカプセルが 1 回の経口投与で投与されます。
他の名前：
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実験的：Treatment Sequence 2
Treatment sequence 2 consisted of three dosing periods in which patients received single oral doses of placebo, 500 mg, and 250 mg of CK-2017357, in that order, with approximately one week between each dose.
Each patient acted as their own control, as all doses were represented in each treatment sequence.
|
単回経口投与として投与されるカプセル中の対応するプラセボ。
単回経口投与として投与されるカプセル中の 250 mg CK-2017357。
他の名前：
500 mg CK-2017357 のカプセルが 1 回の経口投与で投与されます。
他の名前：
|
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実験的：Treatment Sequence 3
Treatment sequence 3 consisted of three dosing periods in which patients received single oral doses of 250 mg, placebo and 500 mg of CK-2017357, in that order, with approximately one week between each dose.
Each patient acted as their own control, as all doses were represented in each treatment sequence.
|
単回経口投与として投与されるカプセル中の対応するプラセボ。
単回経口投与として投与されるカプセル中の 250 mg CK-2017357。
他の名前：
500 mg CK-2017357 のカプセルが 1 回の経口投与で投与されます。
他の名前：
|
|
実験的：Treatment Sequence 4
Treatment sequence 4 consisted of three dosing periods in which patients received single oral doses of 250 mg, 500 mg and placebo of CK-2017357, in that order, with approximately one week between each dose.
Each patient acted as their own control, as all doses were represented in each treatment sequence.
|
単回経口投与として投与されるカプセル中の対応するプラセボ。
単回経口投与として投与されるカプセル中の 250 mg CK-2017357。
他の名前：
500 mg CK-2017357 のカプセルが 1 回の経口投与で投与されます。
他の名前：
|
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実験的：Treatment Sequence 5
Treatment sequence 5 consisted of three dosing periods in which patients received single oral doses of 500 mg, placebo, and 250 mg of CK-2017357, in that order, with approximately one week between each dose.
Each patient acted as their own control, as all doses were represented in each treatment sequence.
|
単回経口投与として投与されるカプセル中の対応するプラセボ。
単回経口投与として投与されるカプセル中の 250 mg CK-2017357。
他の名前：
500 mg CK-2017357 のカプセルが 1 回の経口投与で投与されます。
他の名前：
|
|
実験的：Treatment Sequence 6
Treatment sequence6 consisted of three dosing periods in which patients received single oral doses of 500 mg, 250 mg, and placebo of CK-2017357, in that order, with approximately one week between each dose.
Each patient acted as their own control, as all doses were represented in each treatment sequence.
|
単回経口投与として投与されるカプセル中の対応するプラセボ。
単回経口投与として投与されるカプセル中の 250 mg CK-2017357。
他の名前：
500 mg CK-2017357 のカプセルが 1 回の経口投与で投与されます。
他の名前：
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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ALSFRS-R
時間枠：2 days
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An instrument for evaluating the functional status of patients with ALS.
Minimum score is 0 and maximum score is 40.
The higher the score the more function is retained.
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2 days
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Maximum grip strength
時間枠：2 days
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Measured using the DynEx Electronic Hand Dynamometer.
Patients asked to squeeze the device with the maximum possible force to establish the maximum voluntary contraction.
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2 days
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Maximum grip strength fatigability
時間枠：2 days
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Handgrip fatigue is measured using the DynEx Electronic Hand Dynamometer.
Patient is asked to squeeze the device until they can no longer stay above 60% of target or 120 seconds.
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2 days
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Shoulder extension fatigue
時間枠：2 days
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Patient is asked to hold one arm outstretched in front of them at a 90 degree angle.
The time the arm falls below 90 degrees for > 2 seconds will be recorded, up to a total evaluation time of 2 minutes.
This is then repeated with the other arm.
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2 days
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Slow Vital Capacity (SVC)
時間枠：2 days
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SVC is measured using the Puritan Bennett Renaissance II Spirometry System and accessories.
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2 days
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Maximum Voluntary Ventilation (MVV)
時間枠：2 days
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MVV is the volume of air that can be exhaled during 12 seconds of rapid deep breathing.
The actual volume is extrapolated to one minute.
the Puritan Bennett Renaissance II Spirometry System and accessories is used for this measurement.
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2 days
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Sniff Inspiratory Pressure (SNIP)
時間枠：2 days
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SNIP is measured at Functional Residual Capacity, the bottom of the tidal breathing cycle, through one plugged nostril while the other remains open using the Micro Medical MicroRPM Respiratory Pressure Meter
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2 days
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Maximum Voluntary Muscle Contraction (MVC)
時間枠：2 days
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MVC is measured using the MicroFET 2 HHD.
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2 days
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Repeated Sub-Maximum Grip Strength Fatigability
時間枠：2 days
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Sub-Maximum Grip Strength Fatigability is measured using the DynEx Electronic Hand.
Dynamometer
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2 days
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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有害事象患者数
時間枠：4週間
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4週間
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Characterize the relationship, if any, between the plasma concentration of CK-2017357 and ALSFRS-R.
時間枠：2 days
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ALSFRS-R assessments will be paired with PK concentrations obtained at or near the same time as the ALSFRS-R assessments and analyzed for concentration related effects.
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2 days
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Characterize the relationship, if any, between the plasma concentration of CK-2017357 and maximum grip strength
時間枠：2 days
|
Maximum grip strength assessments will be paired with PK concentrations obtained at or near the same time as the maximum grip strength assessments and analyzed for concentration related effects.
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2 days
|
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Characterize the relationship, if any, between the plasma concentration of CK-2017357 and maximum grip strength fatigability
時間枠：2 days
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Maximum grip strength fatigability assessments will be paired with PK concentrations obtained at or near the same time as the maximum grip strength fatigability assessments and analyzed for concentration related effects.
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2 days
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Characterize the relationship, if any, between the plasma concentration of CK-2017357 and shoulder extension fatigue
時間枠：2 days
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Shoulder extension fatigue assessments will be paired with PK concentrations obtained at or near the same time as the shoulder extension fatigue assessments and analyzed for concentration related effects.
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2 days
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Characterize the relationship, if any, between the plasma concentration of CK-2017357 and slow vital capacity
時間枠：2 days
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Slow vital capacity assessments will be paired with PK concentrations obtained at or near the same time as the slow vital capacity assessments and analyzed for concentration related effects.
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2 days
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Characterize the relationship, if any, between the plasma concentration of CK-2017357 and maximum voluntary ventilation
時間枠：2 days
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Maximum voluntary ventilation assessments will be paired with PK concentrations obtained at or near the same time as the maximum voluntary ventilation assessments and analyzed for concentration related effects.
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2 days
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Characterize the relationship, if any, between the plasma concentration of CK-2017357 and sniff inspiratory pressure
時間枠：2 days
|
Sniff inspiratory pressure assessments will be paired with PK concentrations obtained at or near the same time as the sniff inspiratory pressure assessments and analyzed for concentration related effects.
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2 days
|
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Characterize the relationship, if any, between the plasma concentration of CK-2017357 and maximum voluntary muscle contraction
時間枠：2 days
|
Maximum voluntary muscle contraction assessments will be paired with PK concentrations obtained at or near the same time as the maximum voluntary muscle contraction assessments and analyzed for concentration related effects.
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2 days
|
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Characterize the relationship, if any, between the plasma concentration of CK-2017357 and repeated sub-maximum grip strength fatigability
時間枠：2 days
|
Repeated sub-maximum grip strength fatigability assessments will be paired with PK concentrations obtained at or near the same time as the repeated sub-maximum grip strength fatigability assessments and analyzed for concentration related effects.
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2 days
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Effect of CK-2017357 on patient determined global functional assessment
時間枠：2 days
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Patients will be asked to assess whether they feel the same, better or worse as compared to how they felt pre-dose
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2 days
|
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Effect of CK-2017357 on investigator determined global functional assessment
時間枠：2 days
|
Investigator will assess whether they the patient appears the same, better or worse as compared to the patient's status at pre-dose
|
2 days
|
協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
捜査官
- スタディチェア：Jeremy M Shefner, MD, PhD、State University of New York - Upstate Medical University
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始
2010年3月1日
一次修了 (実際)
2010年11月1日
研究の完了 (実際)
2010年11月1日
試験登録日
最初に提出
2010年3月16日
QC基準を満たした最初の提出物
2010年3月17日
最初の投稿 (見積もり)
2010年3月18日
学習記録の更新
投稿された最後の更新 (実際)
2019年5月10日
QC基準を満たした最後の更新が送信されました
2019年5月7日
最終確認日
2019年5月1日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。