Safety and Tolerability of Quetiapine in Multiple Sclerosis
Status:
Completed
Trial end date:
2019-07-01
Target enrollment:
Participant gender:
Summary
Study Purpose:
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.
Study Design:
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.