Safety and Tolerability of Quetiapine in Multiple Sclerosis
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|ClinicalTrials.gov Identifier: NCT02087631|
Recruitment Status : Recruiting
First Posted : March 14, 2014
Last Update Posted : May 8, 2018
The purpose of this clinical trial is to determine if extended-release quetiapine in a dose of 300 mg daily is tolerable to people with relapsing remitting and progressive MS. The investigators will also determine if the investigators can increase the dose up to 300 mg daily within 3 days in people with relapsing remitting MS and within 2 weeks in people with progressive MS. The investigators will determine if at least two thirds of study participants tolerate the drug well enough to continue it for 4 weeks. Tolerance will be determined separately for people with relapsing remitting and progressive MS. People with progressive MS may be less tolerant of side effects because of greater underlying brain injury from MS. Alternatively, people with progressive MS may gain more benefit from the improved sleep that usually occurs with use of quetiapine or they may be more willing to tolerate some side effects. This clinical trial will determine the maximally tolerated dose for future trials of this drug.
The number of participants in this study will depend on the tolerability at each dose tested. A maximum of 18 people with relapsing remitting MS and 18 people with primary or secondary progressive MS will be included.
The cohort expansion design (3+3) is used to determine toxicity-based dosing. This design is used in oncology phase I trials as it is guided by patient safety and minimizes the number of participants exposed to toxicity (Ivy et al. 2010). Maximum toxicity is defined as 33% or less. In this model, three patients will comprise the initial cohort. In the absence of DLT treatment may be escalated to the next higher dose in the next group of three patients. However, if one of three patients reaches DLT the cohort is expanded to six patients to verify that the toxicity rate has not exceeded or reached 33%. When the toxicity rate exceeds or reaches 33% in a cohort, this dose is deemed the maximum administered dose and a lower dose will be used in the next group of three patients. Patients with RRMS and progressive MS will be evaluated in separate groups using different dose schedules.
|Condition or disease||Intervention/treatment||Phase|
|Multiple Sclerosis||Drug: Extended-release quetiapine fumarate||Phase 1 Phase 2|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||36 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Dose-finding, Safety and Tolerability Trial of Extended-release Quetiapine in Relapsing-remitting and Progressive Multiple Sclerosis|
|Study Start Date :||December 2014|
|Estimated Primary Completion Date :||December 2018|
|Estimated Study Completion Date :||December 2018|
Extended-release quetiapine fumarate up to 300mg once daily for 4 weeks
Drug: Extended-release quetiapine fumarate
Dosing schedule for RRMS: Group 1: Day 1-3:50 mg Day 4-6:100 mg Day 7-28:150 mg Day 29-30:100mg Day 31-32:50mg; Group 2: Day 1-2:50 mg Day 3-4:150 mg Day 5-6:200 mg Day 7-28:300 mg Day 29-30:250mg Day 31-32:200mg Day 33-34:150mg Day 35-36:100mg Day 37-38:50mg; Group 3: Day 1:50 mg Day 2:100 mg Day 3:200 mg Day 4-28:300 mg Day 29-30:250mg Day 31-32:200mg Day 33-34:150mg Day 35-36:100mg Day 37-38:50mg Dosing schedule for progressive MS: Group 1: Day 1-14: 50 mg Day 15-28: 100 mg Day 29-30: 50mg; Group 2: Day 1-5: 50 mg Day 6-10: 100 mg Day 11-15: 150 mg Day 16-28: 200 mg Day 29-30: 150mg Day 31-32: 100mg Day 33-34: 50mg; Group 3: Day 1-5: 50 mg Day 6-10: 100 mg Day 11-15: 200 mg Day 16-28: 300 mg Day 29-30: 250mg Day 31-32: 200mg Day 33-34: 150mg Day 35-36: 100mg Day 37-38: 50mg
Other Name: Seroquel XR
- Dose-limiting toxicity [ Time Frame: 4 weeks ]The primary outcome is the occurrence of dose-limiting toxicity (DLT). Dose-limiting toxicity for any patient in this study is defined as early discontinuation of quetiapine XR due to an adverse event (AE) that is possibly, probably or definitely due to use of study drug. Patients who discontinue medication due to an AE will still be kept in the trial for safety assessment at weeks 4 and 8. Because of the small number of treated participants anyone who discontinues study drug for a reason or adverse event unrelated to use of the study drug will be excluded from the analysis and replaced. The dose-limiting toxicity will be determined for each group of patients: RRMS and progressive MS by the week 4 visit.
- Adverse events [ Time Frame: 4 weeks ]Secondary objectives are to determine treatment safety and tolerance. This will be determined by adverse event reporting; by measuring the impact of treatment on sleep, fatigue, and depression using validated patient report scales; by determining the occurrence of extrapyramidal function by using the extrapyramidal symptom rating scale; and by measuring the impact on cognition by means of the symbol digit modality test.
- Feasibility [ Time Frame: 8 weeks ]Exploratory outcomes will estimate the frequency of eligibility for future trials of quetiapine, determine the level of interest in this study, and determine the frequency of symptoms that might be helped by quetiapine. This information will help determine the feasibility of recruitment to future studies of quetiapine and determine if symptoms that may be improved with quetiapine are common enough in the target population to include measurement of these outcomes in future trials. Patient interest will be estimated based on the proportion of patients who (1) request additional study information, and (2) give telephone consent for pre-screening, and (3) continue to be willing to participate. The frequency of patient eligibility will be estimated by determining the frequency and reason for screen failure. The frequency of symptoms that may be treated with quetiapine will be determined by the results of the patient reported questionnaires completed during screening.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02087631
|Contact: Luanne M. Metz, MD, FRCPC||(403) firstname.lastname@example.org|
|Contact: Marcus Koch, MD, PhD||(403) email@example.com|
|MS Clinic, Foothills Medical Centre||Recruiting|
|Calgary, Alberta, Canada, T2N 2T9|
|Principal Investigator: Luanne M. Metz, M.D.|
|Principal Investigator:||Luanne M Metz, MD,FRCPC||University of Calgary|