The primary objective is to assess the long-term safety and tolerability of tirasemtiv, inpatients with ALS
ID
Source
Brief title
Condition
- Neuromuscular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective is to assess the long-term safety and tolerability of
tirasemtiv, in patients
with ALS.
Secondary outcome
The secondary objectives are:
* To compare the clinical course of patients who completed treatment with
tirasemtiv in
CY 4031 with those who completed treatment with placebo in CY 4031 during
continued treatment of both groups with tirasemtiv during CY 4033
* To compare the clinical course of patients who completed treatment with
tirasemtiv in
CY 4031 during that study with their clinical course during continued treatment
with
tirasemtiv during CY 4033
* To compare the clinical course of patients who completed treatment with
placebo in
CY 4031 during that study with their clinical course during treatment with
tirasemtiv
during CY 4033
Background summary
CY 4033 is an open-label extension study with the selective fast skeletal
muscle troponin
activator, tirasemtiv, in patients with ALS who finished double-blind study
drug and
completed participation (through Week 56) in the CY 4031 study (VITALITY-ALS).
Study objective
The primary objective is to assess the long-term safety and tolerability of
tirasemtiv, in
patients with ALS
Study design
Following enrollment, patients will begin dosing of tirasemtiv 125 mg twice
daily
(250 mg/day) for a period of 4 weeks and will titrate to their tolerated dose,
the maximum
dose being 250 mg twice daily (500 mg/day). The Principal Investigator, or
designee with prescriptive authority in their local jurisdiction, may decide to
up-titrate, maintain dose, or
down-titrate the patient to the previously tolerated dose of tirasemtiv.
Patient clinic visits will occur at Day 1, Week 4, Week 8, Week 12, Week 24,
Week 36,
Week 48, and every 12 weeks thereafter. Patients will be contacted by phone to
assess their
tolerability at Week 2, Week 6, and Week 10. If a patient decides to
discontinue tirasemtiv,
the patient will come into the clinic for the Tirasemtiv Discontinuation Visit
and the 28 Day
Safety Follow-up Visit if the patient is able; otherwise the patient will be
contacted by
phone for these visits.
Intervention
Following enrollment, patients will begin dosing of tirasemtiv 125 mg twice
daily (250 mg/day) for a period of 4 weeks and will titrate to their tolerated
dose, the maximum dose being 250 mg twice daily (500 mg/day). The Principal
Investigator, or designee with prescriptive authority in their local
jurisdiction, may decide to up-titrate, maintain dose, or down-titrate the
patient to the previously tolerated dose of tirasemtiv.
Study burden and risks
Ernstige bijwerkingen (SAE's) tijdens de dubbelblinde behandeling kwamen vaker
voor bij tirasemtiv dan bij placebo (9,0% vs. 5,4%). De meest voorkomende
ernstige bijwerking was respiratoire insufficiëntie, die was opgetreden bij één
patiënt op tirasemtiv en drie patiënten op placebo, terwijl verwarde toestand
en delirium waren opgetreden bij twee patiënten op tirasemtiv en geen van de
patiënten op placebo. Van de patiënten die ten minste één dosis van het
dubbelblinde studiemiddel kregen, trokken meer patiënten op tirasemtiv zich
terug uit het onderzoek na randomisatie dan patienten op placebo
(respectievelijk 97 versus 26 patiënten). Bijwerkingen (AE's) die vaker bij
tirasemtiv voorkwamen dan bij placebo (> 10% verschil) waren duizeligheid
(50,8% versus 19,7%), vermoeidheid (33,2% vs. 14,2%) en misselijkheid (21,9%
vs. 7,8%).
Patiënten op tirasemtiv verloren meer gewicht dan de patiënten op placebo
(verandering vanaf baseline tot week 12: -1,70 kg vs. -0,79 kg; p = 0,006).
Gewichtsverlies was significant groter bij patiënten met gastrointestinale
bijwerkingen (bijvoorbeeld misselijkheid en verminderde eetlust) bij beide
behandelingen. Echter, dergelijke bijwerkingen kwamen vaker bij tirasemtiv dan
bij placebo (43,5% versus 25,8%).
pag. 16 van Protocol 1.0 13Jul2016
East Grand Avenue 280
South San Francisco, California 94080
US
East Grand Avenue 280
South San Francisco, California 94080
US
Listed location countries
Age
Inclusion criteria
1. Able to comprehend and willing to sign an Informed Consent Form (ICF). If verbal consent is given, a Legal Designee of the patient must sign the ICF form;2. Completed participation on study drug and the Follow-Up Visit in the CY 4031 study;3. Male patients, who have not had a vasectomy AND confirmed zero sperm count, must agree for the duration of their participation in the study to either:;a. Use a condom during sexual intercourse with female partners who are of childbearing potential (i.e., following menarche until post-menopausal if not anatomically and physiologically incapable of becoming pregnant) AND to have female partners use a highly effective means of contraception (see below):;OR;b. Abstain from sexual intercourse during participation in the study. ;4. Female patients who are not post-menopausal (* 1 year) or sterilized, must:;a. Not be breastfeeding;b. Have a negative pregnancy test;c. Have no intention to become pregnant during participation in the study,;AND;d. Practice sexual abstinence, defined as refraining from intercourse during the duration of the study OR if male partners are not vasectomized with a confirmed zero sperm count, require use of a condom AND use of a highly effective contraceptive measure, for the duration of the study such as:;* Combined (estrogen and progestogen containing) oral, intravaginal, or transdermal hormonal contraception associated with inhibition of ovulation;* Progestogen-only oral, injectable, or implantable hormonal contraception associated with inhibition of ovulation;* Intrauterine device (IUD);* Intrauterine hormone-releasing system (IUS);* Bilateral tubal occlusion
Exclusion criteria
1. Has a diaphragm pacing system (DPS) at study entry or anticipate DPS placement during the course of the study;2. Has taken any investigational study drug (other than tirasemtiv) prior to dosing, within 30 days or five half-lives of the prior agent, whichever is greater;3. Use of tizanidine and theophylline-containing medications during study participation;4. Participation or planning to participate in another clinical trial involving stem cell therapy for the treatment of ALS or another investigational drug
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2016-002629-13-NL |
| CCMO | NL59871.041.17 |