GAMES-PILOT: Glyburide Advantage in Malignant Edema and Stroke Pilot

• Sponsor: Biogen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01268683
• Collaborator: University of Maryland, College Park (Other), Massachusetts General Hospital (Other)
• Enrollment: 10
• Locations: 4
• Arm: 1
• Actual Duration (Months): 12.4
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The primary objective of this study is to assess the feasibility of enrolling, evaluating, and treating with glyburide for injection severe anterior circulation ischemic stroke participants, whether or not treated with standard of care intravenous (IV) recombinant tissue plasminogen activator (rtPA). Participants must be between 18-80 years of age, must have a baseline diffusion weighted image (DWI) lesion volume 82 -210 centimeters cubed (cm3), and time from symptom onset to start of study infusion must be ≤10 hour(hr). The secondary objectives are to assess the initial safety and tolerability, and pharmacokinetics (PK) /pharmacodynamics (PD) of glyburide in severe stroke participants, as well as to compare the clinical and magnetic resonance imaging (MRI) outcome data to benchmark data derived from published literature.

Condition or Disease	Intervention/Treatment	Phase
Ischemic Stroke	Drug: Glyburide for Injection	Phase 1/Phase 2

Detailed Description

This is a multi-center, prospective, open label, phase IIa trial of glyburide for injection in 10 participants with a severe anterior circulation ischemic stroke who are likely to experience clinically significant brain swelling.

Participants will receive glyburide, delivered as an IV bolus followed by an IV infusion for 72 hours.

Participants will have a baseline (pretreatment) MRI scan as standard of care, and three follow up MRI scans (at 24+12 hours, 48+12 hours, and 72±12 hours). Since recanalization may have an effect on outcome, the results of vascular studies, obtained as part of standard of care and defined as CTA, MRA or catheter angiography of the head and neck, will be recorded. Additionally, clinical endpoints such as the National Institutes of Health Stroke Scale (NIHSS), Glasgow Coma Scale (GCS) and Full Outline of UnResponsiveness Score (FOUR) Score (baseline, 24±12 hour, 48±12 hour, 72±12 hour and 7±1 days) and Modified Rankin Scale (mRS) (30±5 days and 90±7 days) will be assessed. Safety parameters will be assessed through Day 7 or discharge (whichever is sooner), and then again at Day 30±5 and Day 90±7.

Study participation is expected to last 90±7 days.

This study was previously posted by Remedy Pharmaceuticals, Inc. and has since been acquired by Biogen.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multi-Center, Prospective, Open Label, Phase IIa Trial of RP-1127 (Glyburide for Injection) in Patients With a Severe Anterior Circulation Ischemic Stroke Who Are Likely to Experience Clinically Significant Brain Swelling.
• Actual Study Start Date: May 26, 2011
• Actual Primary Completion Date: Jun 7, 2012
• Actual Study Completion Date: Jun 7, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Glyburide for Injection This arm is administered a glyburide bolus followed by continuous infusion of glyburide for 72 hours	Drug: Glyburide for Injection; Administered as specified in the treatment arm.; Other Names: RP-1127 glibenclamide glybenclamide

Outcome Measures

Primary Outcome Measures

1. Rate of Enrollment [Day 1]

   The number of months to enroll 10 participants.

2. Percentage of Enrolled Participants to Screened Participants [Day 1]

3. Percentage of Participants Completing 90-Day Follow-Up [Day 90]

4. Percentage of Dose Reductions/ Dose Suspensions [Up to Day 3]

5. Percentage of Participants With All Four MRI Assessments Per Protocol [Up to Day 3]

6. Number of MRI Assessments Per Participant [Up to Day 3]

7. Percentage of Participants Requiring One or More Hypoglycemia Treatments [Up to Day 4]

8. Percentage of Participants With Pre-specified Adverse Events Associated With Glyburide According to Protocol [Up to Day 4]

Secondary Outcome Measures

1. Number of Participants With Adverse Events and Serious Adverse Events [Up to Day 90]

   Adverse Events (AE's) of special interest (cardiac events, difficulty controlling blood sugar, liver problems, and blood disorders, including anemia) will be followed for 30 days and all Severe Adverse Events (SAE's) will be followed for 90 days. SAE's and AE's were reviewed, and the number of participants with unanticipated adverse events, or drug-related SAE's were assessed.

2. Infarcted Hemisphere Volume [Baseline, Day 1, Day 2, and Day 3]

3. Absolute Diffusion Weighted Imaging (DWI) Lesion Volume [Baseline, Day 1, Day 2, and Day 3]

4. Change From Baseline in DWI Lesion Volume [Baseline, Day 1, Day 2, and Day 3 (Day 3 reported)]

5. Midline Shift [Baseline, Day 1, Day 2, and Day 3]

6. Ipsilateral Ventricle Volume [Baseline, Day 1, Day 2, and Day 3]

7. Frequency of Hemorrhagic Events [Day 1, Day 2, and Day 3]

8. National Institute of Health Stroke Scale (NIHSS) Score [Baseline, Day 1, Day 2, Day 3, and Day 7]

   The NIHSS is composed of 11 categories, each of which is scored between 0 and 4. A score of 0 indicates normal function, a higher score indicates more impairment. Category scores are summed to generate the total NIHSS score (possibles scores range from 0-42).

9. Glasgow Coma Scale (GCS) Score [Baseline, Day 1, Day 2, Day 3, and Day 7]

   The GCS is scored on a scale between 3 and 15 (3 = the worst, and 15 = best). It is composed of three parameters : Best Eye Response (scored on a scale of 1-4), Best Verbal Response (scored on a scale of 1-5), Best Motor Response (scored on a scale of 1-6)

10. Full Outline of UnResponsiveness (FOUR) Score [Baseline, Day 1, Day 2, Day 3, and Day 7]

    The FOUR Score is a 17-point scale (with potential scores ranging from 0 - 16). Decreasing FOUR Score is associated with worsening level of consciousness. The FOUR Score assesses four domains of neurological function: eye responses, motor responses, brainstem reflexes, and breathing pattern.

11. Number of Participants Requiring Decompressive Craniectomy (DC) [Up to Day 90]

12. Number of Participants With a Modified Rankin Scale (mRS) Score ≤ 4 [Day 30, Day 90]

    The mRS scale runs from 0-6, the scoring is as follows: 0 - No symptoms, 1 - No significant disability, 2 - Slight disability, 3 - Moderate disability, 4 - Moderately severe disability, 5 - Severe disability, 6 - Dead

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• A clinical diagnosis of acute ischemic stroke in the MCA or MCA/ACA territory.

• Pre-morbid mRS 0 - 1.

• A baseline DWI lesion between 82 cm3 and 210 cm3 on MRI.

• Patients treated with IV rtPA should meet established criteria for IV rtPA administration in the 0-3 and 3-4.5 hr time periods, respectively.

• The time to the start of infusion of study compound must be ≤ 10 hr after time of symptom onset

• Age ≥18 years and ≤70 years.

• Provision of written informed consent by the patient or from a legally authorized representative according to institutional guidelines and national regulations.

Key Exclusion Criteria:

• Evidence from imaging or pre-enrollment investigation of any diagnosis other than acute ischemic stroke likely to cause the presenting symptoms and signs.

• Commitment to decompressive craniectomy (DC) prior to enrollment, or follow-ing enrollment and prior to start of study compound.

• Treatment with IA rtPA or by mechanical means for clot disruption or with hypo-thermia.

• Patients unable to tolerate MRI scanning, e.g. those with pacemakers or automatic defibrillators.

• Pre-morbid mRS ≥ 2.

• Clinical signs of herniation, e.g. one or two dilated, fixed pupils; unconsciousness (i.e., ≥ 2 on item 1a on the NIHSS); loss of other brain stem reflexes attributable to herniation according to the investigator's judgment.

• CT or MRI evidence of hemorrhage or anteroseptal/pineal shift greater ≥2 mm prior to enrollment.

• Rapidly improving symptoms.

• Severe renal disorder from the patient's history (e.g. dialysis) or eGFR of < 30 mL/min/1.73 m2.

• Severe liver disease or ALT, AST, or bilirubin >2 times normal.

• Blood glucose <55 mg/dL at enrollment or immediately prior to administration of RP-1127, or a clinically significant history of hypoglycemia.

• Diagnosis of decompensated heart failure (e.g. clinical diagnosis of pulmonary edema, chest x-ray consistent with heart failure, tachypnea > 20, etc.)

• Sulfonylurea treatment within 30 days.

• Known allergy to sulfa or specific allergy to sulfonylurea drugs.

• Known G6PD enzyme deficiency.

• Pregnancy or breast-feeding. Women must be either post-menopausal (judged by the investigator), permanently sterilized or, if of childbearing age, must have a negative test for pregnancy obtained before enrollment.

• Patients already enrolled in a non-observation-only stroke study, or with life-expectancy <3 months not related to current stroke, or those unlikely to be com-pliant with follow up.

• Patients who, in the opinion of the investigator, are not suitable for the study (reason to be documented).

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rush University Medical Center	Chicago	Illinois	United States	60612
2	University of Maryland Medical Center	Baltimore	Maryland	United States
3	Massachusetts General Hospital	Boston	Massachusetts	United States
4	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15213

Sponsors and Collaborators

• Biogen
• University of Maryland, College Park
• Massachusetts General Hospital

Investigators

• Study Director: Medical Director, Biogen

Study Documents (Full-Text)

None provided.

More Information

Publications

• Kimberly WT, Battey TW, Pham L, Wu O, Yoo AJ, Furie KL, Singhal AB, Elm JJ, Stern BJ, Sheth KN. Glyburide is associated with attenuated vasogenic edema in stroke patients. Neurocrit Care. 2014 Apr;20(2):193-201. doi: 10.1007/s12028-013-9917-z.
• Sheth KN, Kimberly WT, Elm JJ, Kent TA, Yoo AJ, Thomalla G, Campbell B, Donnan GA, Davis SM, Albers GW, Jacobson S, del Zoppo G, Simard JM, Stern BJ, Mandava P. Exploratory analysis of glyburide as a novel therapy for preventing brain swelling. Neurocrit Care. 2014 Aug;21(1):43-51. doi: 10.1007/s12028-014-9970-2.

• Responsible Party: Biogen
• ClinicalTrials.gov Identifier: NCT01268683
• Other Study ID Numbers: RPI 201
• First Posted: Dec 31, 2010
• Last Update Posted: Aug 6, 2021
• Last Verified: Aug 1, 2021

• Additional relevant MeSH terms: Stroke; Ischemic Stroke; Glyburide

Study Results

Participant Flow

Recruitment Details	Between February 2011, and May 2012, ten subjects were enrolled and treated at University of Maryland and the Massachusetts General Hospital within 9.6 months at 2 sites.

Arm/Group Title	RP-1127 (Glyburide for Injection)
Arm/Group Description	RP-1127 (Glyburide for injection) : Bolus plus 72 hour IV infusion
Period Title: Overall Study
STARTED	10
COMPLETED	8
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	RP-1127 (Glyburide for Injection)
Arm/Group Description	RP-1127 (Glyburide for injection) : Bolus plus 72 hour IV infusion
Overall Participants	10
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	7 70%
>=65 years	3 30%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	50.5
Sex: Female, Male (Count of Participants)
Female	7 70%
Male	3 30%
Region of Enrollment (Count of Participants)
United States	10 100%

Outcome Measures

1. Primary Outcome

Title	Rate of Enrollment
Description	The number of months to enroll 10 participants.
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RP-1127 (Glyburide for Injection)
Arm/Group Description	RP-1127 (Glyburide for injection) : Bolus plus 72 hour IV infusion
Measure Participants	10
Number [Months]	9.6

2. Primary Outcome

Title	Percentage of Enrolled Participants to Screened Participants
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RP-1127 (Glyburide for Injection)
Arm/Group Description	RP-1127 (Glyburide for injection) : Bolus plus 72 hour IV infusion
Measure Participants	175
Number [Percentage of Participants]	5.7 57%

3. Primary Outcome

Title	Percentage of Participants Completing 90-Day Follow-Up
Time Frame	Day 90

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RP-1127 (Glyburide for Injection)
Arm/Group Description	RP-1127 (Glyburide for injection) : Bolus plus 72 hour IV infusion
Measure Participants	10
Number [Percentage of Participants]	80 800%

4. Primary Outcome

Title	Percentage of Dose Reductions/ Dose Suspensions
Time Frame	Up to Day 3

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RP-1127 (Glyburide for Injection)
Arm/Group Description	RP-1127 (Glyburide for injection) : Bolus plus 72 hour IV infusion
Measure Participants	10
Number [Percentage of Participants]	0 0%

5. Primary Outcome

Title	Percentage of Participants With All Four MRI Assessments Per Protocol
Time Frame	Up to Day 3

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RP-1127 (Glyburide for Injection)
Arm/Group Description	RP-1127 (Glyburide for injection) : Bolus plus 72 hour IV infusion
Measure Participants	10
Number [Percentage of Participants]	90 900%

6. Primary Outcome

Title	Number of MRI Assessments Per Participant
Time Frame	Up to Day 3

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RP-1127 (Glyburide for Injection)
Arm/Group Description	RP-1127 (Glyburide for injection) : Bolus plus 72 hour IV infusion
Measure Participants	10
Mean (Full Range) [Number of MRIs]	3.9

7. Primary Outcome

Title	Percentage of Participants Requiring One or More Hypoglycemia Treatments
Time Frame	Up to Day 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RP-1127 (Glyburide for Injection)
Arm/Group Description	RP-1127 (Glyburide for injection) : Bolus plus 72 hour IV infusion
Measure Participants	10
Number [Percentage of Participants]	0 0%

8. Primary Outcome

Title	Percentage of Participants With Pre-specified Adverse Events Associated With Glyburide According to Protocol
Time Frame	Up to Day 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RP-1127 (Glyburide for Injection)
Arm/Group Description	RP-1127 (Glyburide for injection) : Bolus plus 72 hour IV infusion
Measure Participants	10
Number [Percentage of Participants]	0 0%

9. Secondary Outcome

Title	Number of Participants With Adverse Events and Serious Adverse Events
Description	Adverse Events (AE's) of special interest (cardiac events, difficulty controlling blood sugar, liver problems, and blood disorders, including anemia) will be followed for 30 days and all Severe Adverse Events (SAE's) will be followed for 90 days. SAE's and AE's were reviewed, and the number of participants with unanticipated adverse events, or drug-related SAE's were assessed.
Time Frame	Up to Day 90

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RP-1127 (Glyburide for Injection)
Arm/Group Description	RP-1127 (Glyburide for injection) : Bolus plus 72 hour IV infusion
Measure Participants	10
Adverse Events	10 100%
Serious Adverse Events	3 30%

10. Secondary Outcome

Title	Infarcted Hemisphere Volume
Time Frame	Baseline, Day 1, Day 2, and Day 3

Outcome Measure Data

Analysis Population Description

The number analyzed varies due to only MRIs of good quality being analyzed.

Arm/Group Title	RP-1127 (Glyburide for Injection)
Arm/Group Description	RP-1127 (Glyburide for injection) : Bolus plus 72 hour IV infusion
Measure Participants	10
Baseline	135.20 (27.19)
Day 1	156.78 (35.09)
Day 2	165.38 (34.17)
Day 3	181.71 (33.90)

11. Secondary Outcome

Title	Absolute Diffusion Weighted Imaging (DWI) Lesion Volume
Time Frame	Baseline, Day 1, Day 2, and Day 3

Outcome Measure Data

Analysis Population Description

The number analyzed varies due to only MRIs of good quality being analyzed.

Arm/Group Title	RP-1127 (Glyburide for Injection)
Arm/Group Description	RP-1127 (Glyburide for injection) : Bolus plus 72 hour IV infusion
Measure Participants	10
Baseline	101.76 (22.57)
Day 1	141.62 (44.05)
Day 2	152.31 (49.26)
Day 3	169.73 (54.28)

12. Secondary Outcome

Title	Change From Baseline in DWI Lesion Volume
Time Frame	Baseline, Day 1, Day 2, and Day 3 (Day 3 reported)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RP-1127 (Glyburide for Injection)
Arm/Group Description	RP-1127 (Glyburide for injection) : Bolus plus 72 hour IV infusion
Measure Participants	10
Mean (Standard Deviation) [Cm^3]	60.30 (41.37)

13. Secondary Outcome

Title	Midline Shift
Time Frame	Baseline, Day 1, Day 2, and Day 3

Outcome Measure Data

Analysis Population Description

The number analyzed varies due to only MRIs of good quality being analyzed.

Arm/Group Title	RP-1127 (Glyburide for Injection)
Arm/Group Description	RP-1127 (Glyburide for injection) : Bolus plus 72 hour IV infusion
Measure Participants	10
Baseline	0.56 (1.13)
Day 1	2.00 (2.29)
Day 2	2.63 (1.41)
Day 3	2.50 (2.17)

14. Secondary Outcome

Title	Ipsilateral Ventricle Volume
Time Frame	Baseline, Day 1, Day 2, and Day 3

Outcome Measure Data

Analysis Population Description

The number analyzed varies due to only MRIs of good quality being analyzed.

Arm/Group Title	RP-1127 (Glyburide for Injection)
Arm/Group Description	RP-1127 (Glyburide for injection) : Bolus plus 72 hour IV infusion
Measure Participants	10
Baseline	11.78 (5.98)
Day 1	9.25 (4.74)
Day 2	8.92 (4.30)
Day 3	10.07 (6.38)

15. Secondary Outcome

Title	Frequency of Hemorrhagic Events
Time Frame	Day 1, Day 2, and Day 3

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RP-1127 (Glyburide for Injection)
Arm/Group Description	RP-1127 (Glyburide for injection) : Bolus plus 72 hour IV infusion
Measure Participants	10
Hemorrhagic Infarction Type 1	3
Hemorrhagic Infarction Type 2	8
Parenchymal Hematoma Type 1	0
Parenchymal Hematoma Type 2	0

16. Secondary Outcome

Title	National Institute of Health Stroke Scale (NIHSS) Score
Description	The NIHSS is composed of 11 categories, each of which is scored between 0 and 4. A score of 0 indicates normal function, a higher score indicates more impairment. Category scores are summed to generate the total NIHSS score (possibles scores range from 0-42).
Time Frame	Baseline, Day 1, Day 2, Day 3, and Day 7

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RP-1127 (Glyburide for Injection)
Arm/Group Description	RP-1127 (Glyburide for injection) : Bolus plus 72 hour IV infusion
Measure Participants	10
Baseline	17.8 (5.92)
Day 1	18.4 (8.47)
Day 2	15.6 (5.42)
Day 3	16.2 (5.35)
Day 7	13.9 (5.51)

17. Secondary Outcome

Title	Glasgow Coma Scale (GCS) Score
Description	The GCS is scored on a scale between 3 and 15 (3 = the worst, and 15 = best). It is composed of three parameters : Best Eye Response (scored on a scale of 1-4), Best Verbal Response (scored on a scale of 1-5), Best Motor Response (scored on a scale of 1-6)
Time Frame	Baseline, Day 1, Day 2, Day 3, and Day 7

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RP-1127 (Glyburide for Injection)
Arm/Group Description	RP-1127 (Glyburide for injection) : Bolus plus 72 hour IV infusion
Measure Participants	10
Baseline	12.5 (2.51)
Day 1	11.9 (2.64)
Day 2	12.5 (1.96)
Day 3	12.8 (2.20)
Day 7	13.5 (1.58)

18. Secondary Outcome

Title	Full Outline of UnResponsiveness (FOUR) Score
Description	The FOUR Score is a 17-point scale (with potential scores ranging from 0 - 16). Decreasing FOUR Score is associated with worsening level of consciousness. The FOUR Score assesses four domains of neurological function: eye responses, motor responses, brainstem reflexes, and breathing pattern.
Time Frame	Baseline, Day 1, Day 2, Day 3, and Day 7

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RP-1127 (Glyburide for Injection)
Arm/Group Description	RP-1127 (Glyburide for injection) : Bolus plus 72 hour IV infusion
Measure Participants	10
Baseline	15.1 (1.10)
Day 1	14.5 (2.32)
Day 2	14.6 (2.27)
Day 3	14.6 (1.65)
Day 7	14.8 (1.99)

19. Secondary Outcome

Title	Number of Participants Requiring Decompressive Craniectomy (DC)
Time Frame	Up to Day 90

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RP-1127 (Glyburide for Injection)
Arm/Group Description	RP-1127 (Glyburide for injection) : Bolus plus 72 hour IV infusion
Measure Participants	10
Number [Number of Participants]	2 20%

20. Secondary Outcome

Title	Number of Participants With a Modified Rankin Scale (mRS) Score ≤ 4
Description	The mRS scale runs from 0-6, the scoring is as follows: 0 - No symptoms, 1 - No significant disability, 2 - Slight disability, 3 - Moderate disability, 4 - Moderately severe disability, 5 - Severe disability, 6 - Dead
Time Frame	Day 30, Day 90

Outcome Measure Data

Analysis Population Description

The number analyzed varies due to participants not completing follow up.

Arm/Group Title	RP-1127 (Glyburide for Injection)
Arm/Group Description	RP-1127 (Glyburide for injection) : Bolus plus 72 hour IV infusion
Measure Participants	10
Day 30	9 90%
Day 90	8 80%

Adverse Events

Time Frame	Up to 90 Days
Arm/Group Title	RP-1127 (Glyburide for Injection)
Arm/Group Description	RP-1127 (Glyburide for injection) : Bolus plus 72 hour IV infusion
All Cause Mortality
	RP-1127 (Glyburide for Injection)
	Affected / at Risk (%)	# Events
Total	1/10 (10%)
Serious Adverse Events
	RP-1127 (Glyburide for Injection)
	Affected / at Risk (%)	# Events
Total	3/10 (30%)
Metabolism and nutrition disorders
Dehydration	1/10 (10%)
Nervous system disorders
Brain herniation	1/10 (10%)
Cerebrovascular accident	1/10 (10%)
Respiratory, thoracic and mediastinal disorders
Respiratory failure	1/10 (10%)
Vascular disorders
Hypotension	1/10 (10%)
Other (Not Including Serious) Adverse Events
	RP-1127 (Glyburide for Injection)
	Affected / at Risk (%)	# Events
Total	10/10 (100%)
Cardiac disorders
Acute myocardial infarction	1/10 (10%)
Endocrine disorders
Hypercalcaemia	1/10 (10%)
Eye disorders
Dry eyes	1/10 (10%)
Gastrointestinal disorders
Constipation	2/10 (20%)
Dry mouth	1/10 (10%)
Dysphagia	1/10 (10%)
Nausea	4/10 (40%)
General disorders
Pyrexia	1/10 (10%)
Pain	5/10 (50%)
Infections and infestations
Staphylococcal bacteraemia	1/10 (10%)
Urinary tract infection	4/10 (40%)
Injury, poisoning and procedural complications
Open wound	1/10 (10%)
Investigations
Blood glucose decreased	1/10 (10%)
Transaminase increased	1/10 (10%)
Metabolism and nutrition disorders
Hyperkalemia	1/10 (10%)
Hypocalcemia	6/10 (60%)
Hypomagnesemia	8/10 (80%)
Hyponatremia	3/10 (30%)
Hypophosphatemia	4/10 (40%)
Malnutrition	1/10 (10%)
Hypovitaminosis	1/10 (10%)
Fluid overload	2/10 (20%)
Hypokalaemia	8/10 (80%)
Dehydration	1/10 (10%)
Nervous system disorders
Agitation	3/10 (30%)
Headache	1/10 (10%)
Insomnia	1/10 (10%)
Vision blurred	1/10 (10%)
Central pain syndrome	1/10 (10%)
Cerebral haemorrhage	2/10 (20%)
Cerebrovascular accident	1/10 (10%)
Brain herniation	2/10 (20%)
Psychiatric disorders
Alcohol withdrawal syndrome	1/10 (10%)
Anxiety	4/10 (40%)
Depression	1/10 (10%)
Agitation	1/10 (10%)
Renal and urinary disorders
Renal failure chronic	1/10 (10%)
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration	2/10 (20%)
Bronchospasm	2/10 (20%)
Acute pulmonary oedema	1/10 (10%)
Wheezing	1/10 (10%)
Respiratory failure	1/10 (10%)
Vascular disorders
Hypertension	2/10 (20%)
Hypotension	1/10 (10%)

Limitations/Caveats

The trial was a single arm; there is thus no placebo to compare RP-1127 to.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.