Double-blind, Randomised, Placebo-controlled Study to Evaluate the Efficacy and Safety of OSU6162 in the Treatment of Residual Symptoms After Stroke
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Arvid Carlsson Research AB
- Enrollment
- 101
- Locations
- 1
- Primary Endpoint
- Clinical Global Impression of Change (CGI-C)
Study Overview
Brief Summary
Following stroke, a recovery process is promptly initiated, which leads to a partial rehabilitation. However, a number of disabling residual symptoms may persist for years and include mental fatigue, depression, cognitive deficits, neurological problems and more. In the lack of an effective treatment these symptoms will lead to major consequences for the individual and the surrounding society. OSU6162 has in earlier clinical studies of stroke patients shown evidence of a favorable effect on residual symptoms, especially mental fatigue, together with a mild side effect profile.
In this phase II, randomized, placebo-controlled, two-armed study, a 16 week OSU6162 treatment will be compared to an equally long placebo treatment in patients with residual symptoms following stroke.
Detailed Description
Main objectives of this study are to evaluate the efficacy and safety of OSU6162 compared to placebo with respect to treatment response in post stroke patients.
Endpoints:
Primary endpoint is Clinical Global Impression of Change (CGI-C) after 16 weeks of treatment.
Secondary endpoints are:
CGI-C score after 4, 8 and 12 weeks of treatment. FAI; MFS; FSS; BDI; SF-36 scores after 4, 8, 12 and 16 weeks of treatment. Correlation between plasma concentration of OSU6162 and therapeutic response after 4 and 16 weeks of treatment.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
Randomization done externally. IMP codes are contained in sealed envelopes (one envelope for each randomized patient) locked in a drawer at the Gottfries Clinic AB. No envelope is opened prior to the end of the study unless it is critical for the treatment/outcome of an adverse event. In the event of a medical emergency, essential for the clinical management or welfare of the patient, the Investigator may decide to break a patient's treatment code. If the blind is broken, the Investigator must notify the monitor as soon as possible without revealing the patient's study treatment assignment, unless the information is important for the safety of the patients remaining in the study. The Investigator will record the date and reason for breaking the blind for that patient in the hospital records. The coded medicine packages are distributed to the site where the study nurse/investigator are responsible for dispensing the packages to the patients according to the randomization list.
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Signed written informed consent
- •Between 18-80 years
- •Stroke >12 months prior to the start of the study. Patients must have had the location of their stroke evaluated through a CT scan, noted in their hospital notes
- •Anamnestic evidence of post stroke residual symptoms at least 3 months prior to the start of the study
- •At least 10.5 points on Mental Fatigue scale at the screening visit 1 (week -2)
Exclusion Criteria
- •Residual symptoms following other pathologies than stroke
- •Active substance abuse (drug screen taken at visit1)
- •Other serious somatic or psychiatric disease
- •Beck Depression Inventory >30 at visit1 and 2
- •Current pregnancy or breast-feeding, or intention to become pregnant within 3 months after the last dose
- •Female patients of childbearing potential not using adequate contraceptives. Female patients of childbearing potential must, for inclusion, use a highly efficient method of contraception, i.e. a method with a failure rate of less than 1% (e.g. sterilisation, hormone implants, hormone injections, some intrauterine devices, or vasectomy in partner). Male patients must agree to use condoms during the study and for 2 weeks after the end of the study/last dose of IMP, unless their partner is using a highly efficient method of contraception, as described above.
- •Pathologic ECG, as assessed by the investigator. Max QTc time on ECG: 450 ms in men and 460 ms in women
- •Abnormal laboratory values of such severity that participation in the study, in the opinion of the investigator, is questionable
- •Patients who are so debilitated by their disease that they are not assumed to be able to perform the assessments or handle the instruments used for evaluation of effect
- •Current participation in other Clinical trials
- •Previous treatment with OSU6162
- •Clinically significant liver disease which may prevent the patient from completing the study and/or an elevation in either total bilirubin, alkaline phosphatase, AST, ALT of >2 times the laboratory reference
- •Clinically significant renal disease which may prevent the patient from completing the study and/or an elevation in serum creatinine of >1.5 times the laboratory reference.
- •Any surgical or medical condition which, in the opinion of the investigator, might interfere with the absorption, distribution, metabolism or excretion of OSU6162
- •Patients treated with Modiodal, Xyrem, Mirtazapine, Mianserin or metabolic enzyme inhibitors (with the exception of antidepressants other than Mirtazapine and Mianserin) or inducers, or drugs with a narrow treatment window (e.g. warfarin, antiepileptics, cyclosporine) and individually modelled drugs such as lithium.
- •Use of drugs capable of inducing hepatic enzyme metabolism (e.g., barbiturates, rifampicin, carbamazepine, phenytoin, primidone) within 30 days prior to the start of the study (or 5 half-lives of the inducing agent, whichever is longer)
- •Antipsychotic treatment
- •Patients treated with "unstable therapies", i.e., treatments that have not been at the same dose for at least 6 weeks prior to inclusion in this study. The treatment must also remain unchanged during the study period. Insomnia medication and other PRN medications are allowed
- •Use of acute or chronic medications for other medical conditions are allowed based on the investigator's judgement. Occasional use of over-the-counter (OTC) medication is allowed at the investigator's discretion
- •Supplements from health food stores and naturopathic preparations (dietary supplements, natural remedies) are not allowed during the course of the study or 4 weeks before study start.
Arms & Interventions
Arm A
Active substance treatment with OSU6162. Starting dose for all patients in the OSU6162 treatment group is 15 mg BID. The dose is taken orally as one circular coated tablet of 15 mg together with a light meal in the morning and one tablet around lunch unless otherwise agreed upon. In order to aim at optimal dosing of OSU6162, some flexibility is allowed. The investigators are able to modify the dose for individual patients based on how well the treatment is tolerated and how well the patients respond to it. In the case where there is no clear response, the dose can be increased to maximally 30 mg BID (intermediate dosage is allowed) after 4 weeks of treatment; it is also possible to decrease the dose to a lower level (even below 15 mg BID) if a higher dose is not tolerated and/or there is a perceived weakened therapeutic effect with the higher dose. All dose changes will be performed while retaining the blind.
Intervention: OSU 6162 (Drug)
Arm B
Placebo treatment. Starting dose for all patients in the placebo group is one circular coated tablet (with identical appearance to active treatment tablets 15 mg) taken BID, according to the same schedule as active treatment. The dose may be increased or decreased in the same manner as for active treatment.
Intervention: Placebo oral tablet (Drug)
Outcomes
Primary Outcomes
Clinical Global Impression of Change (CGI-C)
Time Frame: Assessment at week 16
The CGI-C is a 7-point scale that requires the clinician to assess how much the patient´s illness has improved or worsened relative to a baseline state at the beginning of the study. CGI-C is rated as: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse. Rating is performed by interviewing the patient to assess function and mental status.
Secondary Outcomes
- Clinical Global Impression of Change (CGI-C)(Assessment at week 4, 8, and 12.)
- Change in Mental Fatigue Scale (MFS)(Assessment at baseline and at week 4, 8, 12, and 16.)
- Change in Becks Depression Inventory (BDI)(Assessment at baseline and at week 4, 8, 12, and 16.)
- Change in Fatigue Severity Scale (FSS)(Assessment at baseline and at week 4, 8, 12, and 16.)
- Change in SF-36 Health Survey(Assessment at baseline and at week 4, 8, 12, and 16.)
- Change in Frenchay Activity Index (FAI)(Assessment at baseline and at week 4, 8, 12, and 16.)