Trial Outcomes & Findings for Modulation of GABA-A Receptors in Parkinson Disease-Transdermal Flumazenil Arm (NCT NCT03440112)
NCT ID: NCT03440112
Last Updated: 2023-01-10
Results Overview
We will use the total Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III - motor scale rating scores to assess motor function. Scale from 0-132, higher scores indicate worse motor outcomes. Outcome measure was collected during dopaminergic medication ON state.
COMPLETED
PHASE1/PHASE2
34 participants
Day 1 (before treatment administration), day 7 (after 7 days of treatment), and day 14 (7 days of treatment discontinuation).
2023-01-10
Participant Flow
5 participants withdrew prior to assignment. 7 participants were recruited for clarithromycin sub-study, which was subsequently dropped in 04/2020 due to concerns related to increased risk of death among the elderly who were taking this antibiotic even for a short time. Only 3 of those participants were randomized and went through study procedures, but the randomization key was not broken so we have no way of knowing what group they were assigned to.
Participant milestones
| Measure |
Transdermal Flumazenil (Active)
Subjects will take 18mg transdermal application every 3-4 hrs dispensed as 3 dispenser bottle clicks of 0.25 ml each, while awake for 3 days then if no side-effects subjects will increase to 36mg transdermal application every 3-4 hrs dispensed as 6 dispenser bottle clicks of 0.25 ml each, while awake.
|
Placebo Cream
Placebo will be taken exactly as the transdermal flumazenil arm: Subjects will take 18mg transdermal application every 3-4 hrs dispensed as 3 dispenser bottle clicks of 0.25 ml each, while awake for 3 days then if no side-effects subjects will increase to 36mg transdermal application every 3-4 hrs dispensed as 6 dispenser bottle clicks of 0.25 ml each, while awake.
|
Oral Clarithromycin (Dropped in 04/2020)
Subjects will take 250 mg twice daily by mouth for 3 days and then - if no side-effects - the dose will increased to 500 mg twice daily by mouth.
|
|---|---|---|---|
|
Overall Study
STARTED
|
11
|
11
|
3
|
|
Overall Study
COMPLETED
|
11
|
11
|
3
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Modulation of GABA-A Receptors in Parkinson Disease-Transdermal Flumazenil Arm
Baseline characteristics by cohort
| Measure |
Transdermal Flumazenil (Active)
n=11 Participants
Added in April 2020. Subjects will take 18mg transdermal application every 3-4 hrs dispensed as 3 dispenser bottle clicks of 0.25 ml each, while awake for 3 days then if no side-effects subjects will increase to 36mg transdermal application every 3-4 hrs dispensed as 6 dispenser bottle clicks of 0.25 ml each, while awake.
|
Placebo Cream
n=11 Participants
Added in April 2020. Placebo will be taken exactly as the transdermal flumazenil arm: Subjects will take 18mg transdermal application every 3-4 hrs dispensed as 3 dispenser bottle clicks of 0.25 ml each, while awake for 3 days then if no side-effects subjects will increase to 36mg transdermal application every 3-4 hrs dispensed as 6 dispenser bottle clicks of 0.25 ml each, while awake.
|
Oral Clarithromycin (Active or Placebo)
n=3 Participants
Discontinued April 2020, study aborted. Subjects will take 250 mg twice daily by mouth for 3 days and then - if no side-effects - the dose will increased to 500 mg twice daily by mouth.
|
Total
n=25 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
72.09 years
STANDARD_DEVIATION 4.41 • n=99 Participants
|
70.27 years
STANDARD_DEVIATION 3.80 • n=107 Participants
|
66.33 years
STANDARD_DEVIATION 5.13 • n=206 Participants
|
70.6 years
STANDARD_DEVIATION 4.43 • n=7 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
5 Participants
n=7 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=99 Participants
|
10 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
20 Participants
n=7 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
11 Participants
n=99 Participants
|
11 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
25 Participants
n=7 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Race (NIH/OMB)
White
|
11 Participants
n=99 Participants
|
11 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
25 Participants
n=7 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Region of Enrollment
United States
|
11 participants
n=99 Participants
|
11 participants
n=107 Participants
|
3 participants
n=206 Participants
|
25 participants
n=7 Participants
|
|
MiniBEST Sensory Subscore
|
5.27 units on a scale
STANDARD_DEVIATION 1.1 • n=99 Participants
|
5.81 units on a scale
STANDARD_DEVIATION 0.40 • n=107 Participants
|
6 units on a scale
STANDARD_DEVIATION 0 • n=206 Participants
|
5.6 units on a scale
STANDARD_DEVIATION 0.82 • n=7 Participants
|
|
Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III
|
45 units on a scale
n=99 Participants
|
41.5 units on a scale
n=107 Participants
|
40.50 units on a scale
n=206 Participants
|
43.5 units on a scale
n=7 Participants
|
PRIMARY outcome
Timeframe: Day 1 (before treatment administration), day 7 (after 7 days of treatment), and day 14 (7 days of treatment discontinuation).Population: Parkinson's disease participants older than 50. Some, but not all, participants in the Clarithromycin arm were randomized, and only few completed study procedures because of premature termination of the trial due to an FDA safety risk warning of Clarithromycin, precluding any meaningful analysis. Consequently, this study arm was replaced by the transdermal Flumazenil arm.
We will use the total Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III - motor scale rating scores to assess motor function. Scale from 0-132, higher scores indicate worse motor outcomes. Outcome measure was collected during dopaminergic medication ON state.
Outcome measures
| Measure |
Transdermal Flumazenil (Active)
n=11 Participants
Subjects will take 18mg transdermal application every 3-4 hrs dispensed as 3 dispenser bottle clicks of 0.25 ml each, while awake for 3 days then if no side-effects subjects will increase to 36mg transdermal application every 3-4 hrs dispensed as 6 dispenser bottle clicks of 0.25 ml each, while awake.
|
Placebo Cream
n=11 Participants
Placebo will be taken exactly as the transdermal flumazenil arm: Subjects will take 18mg transdermal application every 3-4 hrs dispensed as 3 dispenser bottle clicks of 0.25 ml each, while awake for 3 days then if no side-effects subjects will increase to 36mg transdermal application every 3-4 hrs dispensed as 6 dispenser bottle clicks of 0.25 ml each, while awake.
|
Clarithromycin (Active or Placebo)
n=3 Participants
Discontinued April 2020. Subjects will take 250 mg twice daily by mouth for 3 days and then - if no side-effects - the dose will increased to 500 mg twice daily by mouth.
|
|---|---|---|---|
|
Change in Quantitative Biomechanics 1 (Clinical Motor Ratings MDS-UPDRS)
Day 1
|
38 units on a scale
Interval 27.5 to 44.5
|
34 units on a scale
Interval 30.0 to 47.0
|
28 units on a scale
Interval 25.5 to 33.0
|
|
Change in Quantitative Biomechanics 1 (Clinical Motor Ratings MDS-UPDRS)
Day 7
|
36.75 units on a scale
Interval 29.75 to 52.0
|
31.50 units on a scale
Interval 25.375 to 43.375
|
23.50 units on a scale
Interval 21.25 to 26.75
|
|
Change in Quantitative Biomechanics 1 (Clinical Motor Ratings MDS-UPDRS)
Day 14
|
32.75 units on a scale
Interval 26.375 to 47.375
|
34 units on a scale
Interval 29.5 to 40.0
|
22 units on a scale
Interval 19.5 to 23.0
|
SECONDARY outcome
Timeframe: Day 1 (before treatment administration), day 7 (after 7 days of treatment), and day 14 (7 days of treatment discontinuation).Population: Parkinson's disease participants older than 50. Some, but not all, participants in the Clarithromycin arm were randomized, and only few completed study procedures (baseline visit only) because of premature termination of the trial due to an FDA safety risk warning of Clarithromycin, precluding any meaningful analysis. Consequently, this study arm was replaced by the transdermal Flumazenil arm.
MiniBEST sensory subscore measures an individual's ability to maintain balance under conditions of sensory constrain and unstable/inclined standing surface. It is is computed as a sum of MiniBEST items 7, 8, and 9.The score ranges from 0 to 6, with 0 indicating inability to balance under all of the condition, and 6 indicating no difficulty in maintaining balance under any of the conditions (lower score indicates worse balance). Outcome measure was collected during dopaminergic medication ON state.
Outcome measures
| Measure |
Transdermal Flumazenil (Active)
n=11 Participants
Subjects will take 18mg transdermal application every 3-4 hrs dispensed as 3 dispenser bottle clicks of 0.25 ml each, while awake for 3 days then if no side-effects subjects will increase to 36mg transdermal application every 3-4 hrs dispensed as 6 dispenser bottle clicks of 0.25 ml each, while awake.
|
Placebo Cream
n=11 Participants
Placebo will be taken exactly as the transdermal flumazenil arm: Subjects will take 18mg transdermal application every 3-4 hrs dispensed as 3 dispenser bottle clicks of 0.25 ml each, while awake for 3 days then if no side-effects subjects will increase to 36mg transdermal application every 3-4 hrs dispensed as 6 dispenser bottle clicks of 0.25 ml each, while awake.
|
Clarithromycin (Active or Placebo)
n=3 Participants
Discontinued April 2020. Subjects will take 250 mg twice daily by mouth for 3 days and then - if no side-effects - the dose will increased to 500 mg twice daily by mouth.
|
|---|---|---|---|
|
Change in Quantitative Biomechanics 2 (MiniBESTest Dynamic Balance Scale Sensory Subscore)
Day 1
|
5.54 units on a scale
Standard Deviation 0.69
|
6 units on a scale
Standard Deviation 0
|
6 units on a scale
Standard Deviation 0
|
|
Change in Quantitative Biomechanics 2 (MiniBESTest Dynamic Balance Scale Sensory Subscore)
Day 7
|
5.82 units on a scale
Standard Deviation 0.40
|
6 units on a scale
Standard Deviation 0
|
5.67 units on a scale
Standard Deviation 0.58
|
|
Change in Quantitative Biomechanics 2 (MiniBESTest Dynamic Balance Scale Sensory Subscore)
Day 14
|
6 units on a scale
Standard Deviation 0
|
5.82 units on a scale
Standard Deviation 0.60
|
6 units on a scale
Standard Deviation 0
|
Adverse Events
Transdermal Flumazenil (Active)
Placebo Cream
Oral Clarithromycin (Dropped in 04/2020)
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place