Last updated: 11/07/2018 03:32:40
Safety escalating repeat IV, in stroke patientsMAG111539
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: A Single-Blind Study of the Safety, Pharmacokinetics and Pharmacodynamics of Escalating Repeat Doses of GSK249320 in Patients With Stroke
Trial description: The purpose of this study is to is to test increasing repeat doses of GSK249320 compared to placebo in patients with stroke.
Primary purpose:
Other
Trial design:
Parallel Assignment
Masking:
Single (Participant)
Allocation:
Randomized
Primary outcomes:
Number of participants with adverse events (AE) and serious adverse events (SAE)
Timeframe: Up to 112 days
Number of participants with vital signs changes of potential clinical importance
Timeframe: Up to 112 days
Number of participants with Electrocardiogram (ECG) values outside range of potential clinical importance
Timeframe: Up to 112 days
Number of participants with Nerve Conduction Testing (NCT) values
Timeframe: Day 5 and 30 and at early withdrawal
Number of participants with white matter changes and demyelination assessed by magnetic resonance imaging (MRI)
Timeframe: Up to Day 60
Number of participants with abnormal clinical chemistry parameters
Timeframe: Up to Day 112
Number of participants with abnormal hematological parameters
Timeframe: Up to Day 112
Secondary outcomes:
Number of participants with positive antibodies to GSK249320
Timeframe: Day 1, 5, 10, 30, 60, 90 and 112
Mean Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC 0-inf) and Area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration (AUC0-t)
Timeframe: Day 1 (Pre-dose, 1, 3, 6, 12 and 24 hour) and Day 10 (Pre-dose, 1, 3 hour)
Mean Maximum observed concentration (Cmax) and Last observed quantifiable concentration (Ct)
Timeframe: Day 1 (Pre-dose, 1, 3, 6, 12 and 24 hour) and Day 10 (Pre-dose, 1, 3 hour)
Mean time of occurrence of Cmax (tmax) and time of last observed quantifiable concentration (tlast)
Timeframe: Day 1 (Pre-dose, 1, 3, 6, 12 and 24 hour) and Day 10 (Pre-dose, 1, 3 hour)
Mean Terminal phase half-life (t1/2)
Timeframe: Day 1 (Pre-dose, 1, 3, 6, 12 and 24 hour) and Day 10 (Pre-dose, 1, 3 hour)
Mean Terminal phase rate constant ( lambda-Z)
Timeframe: Day 1 (Pre-dose, 1, 3, 6, 12 and 24 hour) and Day 10 (Pre-dose, 1, 3 hour)
Mean Clearance of GSK249320
Timeframe: Day 1 (Pre-dose, 1, 3, 6, 12 and 24 hour) and Day 10 (Pre-dose, 1, 3 hour)
Mean Change in mean gait velocity
Timeframe: Baseline (Day 5), Day 30, 60, 90, 112
Mean Change in Berg Balance Scale (BBS) Total Score
Timeframe: Baseline (Day 5), Day 30, 60, 90 and 112
Mean Change in Total Fugl-Meyer Motor (FM) Assessment
Timeframe: Baseline (Day 5), Day 30 and 112
Mean Change in Total Box and Blocks Transferred on affected side
Timeframe: Baseline (Day 1), Day 30, 60, 90 and 112
Mean Change in Grip Strength on affected side
Timeframe: Baseline (Day 1), Day 30, 60, 90 and 112
Number of participants with Modified Rankin Scale (mRS)
Timeframe: Day 30 and 90
Change from Baseline of National Institutes of Health Stroke Scale (NIHSS)
Timeframe: Baseline (Day 1), Day 10, 30 and 90
Mean Barthel Total Score
Timeframe: Day 30 and 90
Mean Total Montreal Cognitive Assessment (MoCA) Score
Timeframe: Day 5 and 90
Mean Geriatric Depression Scale (GDS)
Timeframe: Day 5 and 90
Mean Change in Transcranial Magnetic Stimulations (TMS) evaluated by Peak to Peak MEP by % Stimulation level
Timeframe: Baseline (Day 1), Day 30 and 112
Serum levels of the S100β protein
Timeframe: Day 1 (Pre-dose, Post dose 1, 6, 24 hour), Day 5
Interventions:
Drug: GSK249320
Drug: PLACEBO
Enrollment:
42
Observational study model:
Not applicable
Primary completion date:
2011-31-01
Time perspective:
Not applicable
Clinical publications:
Cramer S, Abila B, Scott N, Simeoni M, Enney L. Safety, Pharmacokinetics, and Pharmacodynamics of Escalating Repeat Doses of GSK249320 in Patients With Stroke. Stroke. 2013;44(5):1337-1342.
M Malcolm, L. Enney, S. Cramer.Methods for an international randomized clinical trial to investigate the effect of GSK249320 on motor cortex neurophysiology using transcranial magnetic stimulation in survivors of stroke.J Clin Trials.2014;4(6):199
Medical condition
Ischaemic Attack, Transient
Product
refanezumab
Collaborators
Not applicable
Study date(s)
July 2009 to January 2011
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
18 - 90 years
Accepts healthy volunteers
No
- Have a confirmed diagnosis of stroke
- Stroke onset must be within the last 24-72 hours.
- History of a previous symptomatic stroke within 3 months prior to study entry.
- Presence of significant disability prior to the current stroke. Significant disability is defined as having a pre-stroke Rankin score of >2.
Inclusion and exclusion criteria
Inclusion criteria:
- Have a confirmed diagnosis of stroke
- Stroke onset must be within the last 24-72 hours.
- Have a stroke that is either:
- radiologically confirmed to be ischaemic and supratentorial. The diameter of the ischemic lesion is >15mm in any singlle direction or the volume is >4cc. OR
- radiologically confirmed to be an intracerebral hemorrhage that is supratentorial, deep (i.e., blood must not directly contact cerebral cortex) and with minimal or no intraventricular extension. The Intracerebral Hemorrahage (CH) score must be 0-2 and is calculated based on age, Galsgow coma Scale score ad the initial CT or MRI findings for the index stroke. See the SOM for the full calculation procedure.
- Have a total NIHSS score of 3-21.
- Have an upper and/or lower limb deficit defined as:
- Score of 1-3 on the NIHSS Motor Arm question, and palpable and observable voluntary extension or flexion of the fingers. AND/OR b. Score of 1-3 on the NIHSS Motor Leg question
- Aged 18-90, inclusive.
- Male subjects and females of non-child-bearing potential are allowed to participate in this study.
- Females of child-bearing potential are also allowed to participate in this study provided they are using a contraceptive method with a failure rate of <1%.
Exclusion criteria:
- History of a previous symptomatic stroke within 3 months prior to study entry.
- Presence of significant disability prior to the current stroke. Significant disability is defined as having a pre-stroke Rankin score of >2.
- Presence of depression that is active and not adequately controlled such that it interferred with major activities of daily living immediately prior to the current stroke.
- Subjects who are not alert or are unresponsive as defined by a score of 2 or 3 on the NIHSS Level of Consciousness question (question #1a).
- Presence of significant aphasia as likely to confound or interfere with completion of the study assessments.
- Presence of peripheral neuropathy, including diabetic neuropathy, which is clinically active and symptomatic at time of screening.
- Presence of neurological or psychiatric disease, such as dementia or mild cognitive impairment, prior to study entry that is likely to confound clinical evaluations.
- Presence of a demyelinating disease, such as multiple sclerosis.
- Evidence of other chronic co-morbid conditions or unstable acute systemic illnesses which, in the opinion of the investigator, could shorten the subject’s survival or limit his/her ability to complete the study.
- History of sensitivity to heparin or heparin-induced thrombocytopenia.
- Presence of QTcB > 500 msec; or uncorrected QT >600msec (machine or manual over-read) on baseline ECG.
- Contraindication to TMS, such as:
- have metal present, such as hardware or plate on the scalp in the area to which TMS will be applied, implanted cardiac pacemaker, implanted prosthetic heart valve, medication pump or line, metallic implant or clip in the head/neck, electrical, mechanical or magnetic implants, neuro-stimulation device, or orthodontic work involving ferromagnetic materials
- occupation or activity that may cause accidental lodging of ferromagnetic materials or embedded metal fragments in the head. Subjects can be cleared by a head computed tomography scan.
- concomitant use of drugs that substantially lower seizure threshold (e.g., tricyclic antidepressants and neuroleptics)
- known history of seizures or epilepsy
- brain tumor, recent brain injury (within 5 years) associated with definite loss of consciousness, or any history of brain surgery
- Contraindication to MRI, such as:
- have metal present, such as implanted cardiac pacemaker, implanted prosthetic heart valve, medication pump or line, metallic implant or clip in the head/neck, electrical, mechanical or magnetic implants, neuro-stimulation device, or orthodontic work involving ferromagnetic materials, permanent tattooed metallic eye-liner
- occupation or activity that may cause accidental lodging of ferromagnetic materials or embedded metal fragments in the head. Subjects can be cleared by a head computed tomography scan.
- claustrophobia
- Participation in any investigational rehabilitation paradigm targeting stroke recovery during the duration of this study.
- The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer). Pregnant or lactating females.
- Subjects considered unwilling or unable to comply with the procedures and study visit schedule outlined in the protocol.
Trial location(s)
Location
GSK Investigational Site
Detroit, Michigan, United States, 48201
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Mainz, Rheinland-Pfalz, Germany, 55131
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Fort Collins, Colorado, United States, 80524
Status
Study Complete
Location
GSK Investigational Site
Wiesbaden, Hessen, Germany, 65199
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Portland, Oregon, United States, 97239
Status
Study Complete
Location
GSK Investigational Site
Essen, Nordrhein-Westfalen, Germany, 45122
Status
Study Complete
Location
GSK Investigational Site
Koeln, Nordrhein-Westfalen, Germany, 50937
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Ulm, Baden-Wuerttemberg, Germany, 89081
Status
Study Complete
Location
GSK Investigational Site
Los Angeles, California, United States, 90095-6984
Status
Will Be Recruiting
Location
GSK Investigational Site
Hannover, Niedersachsen, Germany, 30625
Status
Study Complete
Location
GSK Investigational Site
Orange, California, United States, 92868-4280
Status
Study Complete
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2011-31-01
Actual study completion date
2011-31-01
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
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