Study Evaluating Efficacy and Safety of OSU6162 in the Treatment of Residual Symptoms After Stroke

NCT04127669 | Completed Phase 2 DMC

• 2 other identifiers: OSU6162DB0032016-003888-19
• Study Type: interventional
• Target: 101
• Locations: 1 country
• Sites: 1

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.

Conditions

Stroke Sequelae

Keywords

residual symptoms; mental fatigue; dopamine stabilizer

Outcome Measures

Primary Outcomes (1)

• Clinical Global Impression of Change (CGI-C)

  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.

  Assessment at week 16

Secondary Outcomes (6)

• Clinical Global Impression of Change (CGI-C)

  Assessment at week 4, 8, and 12.

• Change in Frenchay Activity Index (FAI)

  Assessment at baseline and at week 4, 8, 12, and 16.

• Change in Mental Fatigue Scale (MFS)

  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 Becks Depression Inventory (BDI)

  Assessment at baseline and at week 4, 8, 12, and 16.

Other Outcomes (7)

• Plasma concentrations of OSU6162

  Assessment at week 4 and 16.

• Adverse Events (AE) or Serious Adverse Events (SAE) - safety assessment

  Assessment at baseline and week 2, 4, 6, 8, 10, 12, 14, 16 and 20.

• Physical and neurological examinations - safety assessment

  Assessment at baseline and week 4, 8, 12, 16 and 20.

Study Arms (2)

Arm A

EXPERIMENTAL

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.

Drug: OSU 6162

Arm B

PLACEBO COMPARATOR

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.

Drug: Placebo oral tablet

Interventions

OSU 6162 DRUG

The active ingredient of OSU6162 is the S-enantiomer with the chemical name (S)-3-\[3-(methylsulfonyl)phenyl\]-1-propylpiperidine hydrochloride. The substance is a white powder with a melting point of 177-182°C. Solubility in water is \> 2000 mg/ml. Current laboratory code used is OSU6162-HCl. In trial protocol, OSU6162-HCl is shortened to OSU6162.

Also known as: OSU6162-HCl, PNU-9639 1A

Arm A

Placebo oral tablet DRUG

Circular coated tablet (with identical appearance to active treatment tablets 15 mg).

Arm B

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• Arvid Carlsson Research AB: lead
• Gottfries Clinic AB: collaborator

Study Sites (1)

Gottfries Clinic AB

Gothenburg, SE-43137, Sweden

Location

Related Links

• EU Clinical Trials Register

MeSH Terms

Conditions

Mental Fatigue

Interventions

OSU 6162

Condition Hierarchy (Ancestors)

Fatigue; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavioral Symptoms; Behavior

Study Officials

• Carl-Gerhard Gottfries, Prof.

  Gottfries Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This study is a randomised, placebo-controlled, parallel-group (two-armed) study of 16 weeks' treatment duration, comparing OSU6162 with placebo treatment in patients with residual symptoms after stroke.

Study Record Dates

• First Submitted: October 9, 2019
• First Posted: October 15, 2019
• Study Start: March 20, 2017
• Primary Completion: January 28, 2020
• Study Completion: September 30, 2020
• Last Updated: October 1, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)