Trial Outcomes & Findings for Carbidopa for the Treatment of Excessive Blood Pressure Variability (NCT NCT02553265)
NCT ID: NCT02553265
Last Updated: 2022-02-09
Results Overview
Adverse events defined as: a change in a patient's baseline condition including intercurrent illnesses irrespective of the relationship to carbidopa treatment. This will be monitored primarily with phone calls at weekly intervals. In addition, patients will be asked about adverse events while at the office. Patients will also fill a daily diary with a specific prompts to note any adverse events.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
22 participants
Primary outcome timeframe
Up to 90 days
Results posted on
2022-02-09
Participant Flow
Participant milestones
| Measure |
Low-Dose Carbidopa, Then Placebo, Then High-Dose Carbidopa
Patients received low-dose carbidopa (300 mg/day), matching placebo, then high-dose carbidopa (600 mg/day) in 3 separate 4-week treatment periods. Doses were divided 3x daily, administered 6 hours apart, with a 4-day dose de-escalation and washout period between dose changes. in 3 separate 4-week treatment periods. Doses were divided 3x daily, administered 6 hours apart, with a 4-day dose de-escalation and washout period between dose changes.
|
High-Dose Carbidopa, Then Low-Dose Carbidopa, Then Placebo
Patients received high-dose carbidopa (600 mg/day), low-dose carbidopa (300 mg/day), then matching placebo in 3 separate 4-week treatment periods. Doses were divided 3x daily, administered 6 hours apart, with a 4-day dose de-escalation and washout period between dose changes. in 3 separate 4-week treatment periods. Doses were divided 3x daily, administered 6 hours apart, with a 4-day dose de-escalation and washout period between dose changes.
|
Placebo, Then High-Dose Carbidopa, Then Low-Dose Carbidopa
Patients received matching placebo, high-dose carbidopa (600 mg/day), then low-dose carbidopa (300 mg/day) in 3 separate 4-week treatment periods. Doses were divided 3x daily, administered 6 hours apart, with a 4-day dose de-escalation and washout period between dose changes.
|
|---|---|---|---|
|
Enrollment
STARTED
|
9
|
7
|
6
|
|
Enrollment
COMPLETED
|
9
|
7
|
5
|
|
Enrollment
NOT COMPLETED
|
0
|
0
|
1
|
|
First Intervention (28 Days)
STARTED
|
9
|
7
|
5
|
|
First Intervention (28 Days)
COMPLETED
|
8
|
7
|
4
|
|
First Intervention (28 Days)
NOT COMPLETED
|
1
|
0
|
1
|
|
Second Intervention (28 Days)
STARTED
|
8
|
7
|
4
|
|
Second Intervention (28 Days)
COMPLETED
|
7
|
7
|
4
|
|
Second Intervention (28 Days)
NOT COMPLETED
|
1
|
0
|
0
|
|
Third Intervention (28 Days)
STARTED
|
7
|
7
|
4
|
|
Third Intervention (28 Days)
COMPLETED
|
6
|
7
|
3
|
|
Third Intervention (28 Days)
NOT COMPLETED
|
1
|
0
|
1
|
Reasons for withdrawal
| Measure |
Low-Dose Carbidopa, Then Placebo, Then High-Dose Carbidopa
Patients received low-dose carbidopa (300 mg/day), matching placebo, then high-dose carbidopa (600 mg/day) in 3 separate 4-week treatment periods. Doses were divided 3x daily, administered 6 hours apart, with a 4-day dose de-escalation and washout period between dose changes. in 3 separate 4-week treatment periods. Doses were divided 3x daily, administered 6 hours apart, with a 4-day dose de-escalation and washout period between dose changes.
|
High-Dose Carbidopa, Then Low-Dose Carbidopa, Then Placebo
Patients received high-dose carbidopa (600 mg/day), low-dose carbidopa (300 mg/day), then matching placebo in 3 separate 4-week treatment periods. Doses were divided 3x daily, administered 6 hours apart, with a 4-day dose de-escalation and washout period between dose changes. in 3 separate 4-week treatment periods. Doses were divided 3x daily, administered 6 hours apart, with a 4-day dose de-escalation and washout period between dose changes.
|
Placebo, Then High-Dose Carbidopa, Then Low-Dose Carbidopa
Patients received matching placebo, high-dose carbidopa (600 mg/day), then low-dose carbidopa (300 mg/day) in 3 separate 4-week treatment periods. Doses were divided 3x daily, administered 6 hours apart, with a 4-day dose de-escalation and washout period between dose changes.
|
|---|---|---|---|
|
Enrollment
Death
|
0
|
0
|
1
|
|
First Intervention (28 Days)
Adverse Event
|
1
|
0
|
0
|
|
First Intervention (28 Days)
Withdrawal by Subject
|
0
|
0
|
1
|
|
Second Intervention (28 Days)
Adverse Event
|
1
|
0
|
0
|
|
Third Intervention (28 Days)
Adverse Event
|
1
|
0
|
0
|
|
Third Intervention (28 Days)
Lost to Follow-up
|
0
|
0
|
1
|
Baseline Characteristics
Carbidopa for the Treatment of Excessive Blood Pressure Variability
Baseline characteristics by cohort
| Measure |
Low Dose Carbidopa, High Dose Carbidopa, Placebo
n=22 Participants
This is a 14-week study. Patients will receive, in random order, high dose carbidopa (600mg/day), low dose carbidopa (300 mg/day) or placebo. Between each crossover, there will be a titration down over 2-days followed by a 2-day washout.
Carbidopa Low Dose
Placebo: A placebo containing an inert substance, in capsule form that does not contain an active drug ingredient.
Carbidopa High Dose
|
|---|---|
|
Age, Continuous
|
28 years
n=93 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
22 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
White
|
22 Participants
n=93 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
|
Region of Enrollment
United States
|
22 participants
n=93 Participants
|
PRIMARY outcome
Timeframe: Up to 90 daysAdverse events defined as: a change in a patient's baseline condition including intercurrent illnesses irrespective of the relationship to carbidopa treatment. This will be monitored primarily with phone calls at weekly intervals. In addition, patients will be asked about adverse events while at the office. Patients will also fill a daily diary with a specific prompts to note any adverse events.
Outcome measures
| Measure |
Placebo
n=16 Participants
A placebo containing an inert substance, in capsule form that does not contain an active drug ingredient.
|
Low-Dose Carbidopa
n=16 Participants
300 mg/day
Other Names: Lodosyn ®, DL-α-methyl-α-hydrazino-3, 4-dihydroxyphenyl-propionic acid, HMD, MK-486
|
High-Dose Carbidopa
n=16 Participants
600 mg/day
Other Names: Lodosyn ®, DL-α-methyl-α-hydrazino-3, 4-dihydroxyphenyl-propionic acid, HMD, MK-486
|
|---|---|---|---|
|
Number of Participants Who Reported Adverse Events Related to Study Drug
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Up to 90 daysBody mass measured in kg
Outcome measures
| Measure |
Placebo
n=16 Participants
A placebo containing an inert substance, in capsule form that does not contain an active drug ingredient.
|
Low-Dose Carbidopa
n=16 Participants
300 mg/day
Other Names: Lodosyn ®, DL-α-methyl-α-hydrazino-3, 4-dihydroxyphenyl-propionic acid, HMD, MK-486
|
High-Dose Carbidopa
n=16 Participants
600 mg/day
Other Names: Lodosyn ®, DL-α-methyl-α-hydrazino-3, 4-dihydroxyphenyl-propionic acid, HMD, MK-486
|
|---|---|---|---|
|
Number of Participants With Significant Changes in Body Mass That Resulted in Discontinuation From the Study.
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Up to 90 daysClinically significant changes in the intervals of characteristic electrocardiographic patterns
Outcome measures
| Measure |
Placebo
n=16 Participants
A placebo containing an inert substance, in capsule form that does not contain an active drug ingredient.
|
Low-Dose Carbidopa
n=16 Participants
300 mg/day
Other Names: Lodosyn ®, DL-α-methyl-α-hydrazino-3, 4-dihydroxyphenyl-propionic acid, HMD, MK-486
|
High-Dose Carbidopa
n=16 Participants
600 mg/day
Other Names: Lodosyn ®, DL-α-methyl-α-hydrazino-3, 4-dihydroxyphenyl-propionic acid, HMD, MK-486
|
|---|---|---|---|
|
Number of Participants With Abnormal Electrocardiographic Interval Patterns
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: up to Week 14Patients with FD undergo ambulatory BP monitoring while keeping a detailed log of their activities (sleep/meal-times/medications/posture/symptoms). Variability in blood pressure overtime will be measured by the standard deviation during awake hours
Outcome measures
| Measure |
Placebo
n=16 Participants
A placebo containing an inert substance, in capsule form that does not contain an active drug ingredient.
|
Low-Dose Carbidopa
n=16 Participants
300 mg/day
Other Names: Lodosyn ®, DL-α-methyl-α-hydrazino-3, 4-dihydroxyphenyl-propionic acid, HMD, MK-486
|
High-Dose Carbidopa
n=16 Participants
600 mg/day
Other Names: Lodosyn ®, DL-α-methyl-α-hydrazino-3, 4-dihydroxyphenyl-propionic acid, HMD, MK-486
|
|---|---|---|---|
|
Average Systolic Blood Pressure Variability (Daytime)
|
22.92 mmHg
Standard Deviation 6.13
|
18.71 mmHg
Standard Deviation 4.83
|
16.92 mmHg
Standard Deviation 4.14
|
PRIMARY outcome
Timeframe: Day 1 of treatment periodMaximum blood pressure captured on 24-h ambulatory monitoring
Outcome measures
| Measure |
Placebo
n=16 Participants
A placebo containing an inert substance, in capsule form that does not contain an active drug ingredient.
|
Low-Dose Carbidopa
n=16 Participants
300 mg/day
Other Names: Lodosyn ®, DL-α-methyl-α-hydrazino-3, 4-dihydroxyphenyl-propionic acid, HMD, MK-486
|
High-Dose Carbidopa
n=16 Participants
600 mg/day
Other Names: Lodosyn ®, DL-α-methyl-α-hydrazino-3, 4-dihydroxyphenyl-propionic acid, HMD, MK-486
|
|---|---|---|---|
|
Highest Systolic Blood Pressure
|
175 mmHg
Standard Deviation 27
|
157 mmHg
Standard Deviation 20
|
150 mmHg
Standard Deviation 17
|
PRIMARY outcome
Timeframe: up to Week 14SBP measured in the seated position
Outcome measures
| Measure |
Placebo
n=16 Participants
A placebo containing an inert substance, in capsule form that does not contain an active drug ingredient.
|
Low-Dose Carbidopa
n=16 Participants
300 mg/day
Other Names: Lodosyn ®, DL-α-methyl-α-hydrazino-3, 4-dihydroxyphenyl-propionic acid, HMD, MK-486
|
High-Dose Carbidopa
n=16 Participants
600 mg/day
Other Names: Lodosyn ®, DL-α-methyl-α-hydrazino-3, 4-dihydroxyphenyl-propionic acid, HMD, MK-486
|
|---|---|---|---|
|
Systolic Blood Pressure
|
126 mmHg
Standard Deviation 27
|
126 mmHg
Standard Deviation 18
|
126 mmHg
Standard Deviation 21
|
PRIMARY outcome
Timeframe: up to Week 14Heart rate in the seated position
Outcome measures
| Measure |
Placebo
n=16 Participants
A placebo containing an inert substance, in capsule form that does not contain an active drug ingredient.
|
Low-Dose Carbidopa
n=16 Participants
300 mg/day
Other Names: Lodosyn ®, DL-α-methyl-α-hydrazino-3, 4-dihydroxyphenyl-propionic acid, HMD, MK-486
|
High-Dose Carbidopa
n=16 Participants
600 mg/day
Other Names: Lodosyn ®, DL-α-methyl-α-hydrazino-3, 4-dihydroxyphenyl-propionic acid, HMD, MK-486
|
|---|---|---|---|
|
Heart Rate
|
76 beats per minute (BPM)
Standard Deviation 11
|
72 beats per minute (BPM)
Standard Deviation 13
|
78 beats per minute (BPM)
Standard Deviation 13
|
PRIMARY outcome
Timeframe: Up to 90 daysClinically significant laboratory values include complete blood count (CMC) and metabolic panel related to treatment with carbidopa
Outcome measures
| Measure |
Placebo
n=16 Participants
A placebo containing an inert substance, in capsule form that does not contain an active drug ingredient.
|
Low-Dose Carbidopa
n=16 Participants
300 mg/day
Other Names: Lodosyn ®, DL-α-methyl-α-hydrazino-3, 4-dihydroxyphenyl-propionic acid, HMD, MK-486
|
High-Dose Carbidopa
n=16 Participants
600 mg/day
Other Names: Lodosyn ®, DL-α-methyl-α-hydrazino-3, 4-dihydroxyphenyl-propionic acid, HMD, MK-486
|
|---|---|---|---|
|
Number of Participants Who Displayed Clinical Significant Laboratory Values on CBC or Metabolic Panel
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Up to 90 daysClinically significant values on urinalysis, urine safety parameters related to treatment with carbidopa
Outcome measures
| Measure |
Placebo
n=16 Participants
A placebo containing an inert substance, in capsule form that does not contain an active drug ingredient.
|
Low-Dose Carbidopa
n=16 Participants
300 mg/day
Other Names: Lodosyn ®, DL-α-methyl-α-hydrazino-3, 4-dihydroxyphenyl-propionic acid, HMD, MK-486
|
High-Dose Carbidopa
n=16 Participants
600 mg/day
Other Names: Lodosyn ®, DL-α-methyl-α-hydrazino-3, 4-dihydroxyphenyl-propionic acid, HMD, MK-486
|
|---|---|---|---|
|
Number of Participants Who Displayed Clinically Significant Values in Urine Safety Parameters
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: up to Week 14Lowest blood pressure captured during 3 minutes of standing
Outcome measures
| Measure |
Placebo
n=16 Participants
A placebo containing an inert substance, in capsule form that does not contain an active drug ingredient.
|
Low-Dose Carbidopa
n=16 Participants
300 mg/day
Other Names: Lodosyn ®, DL-α-methyl-α-hydrazino-3, 4-dihydroxyphenyl-propionic acid, HMD, MK-486
|
High-Dose Carbidopa
n=16 Participants
600 mg/day
Other Names: Lodosyn ®, DL-α-methyl-α-hydrazino-3, 4-dihydroxyphenyl-propionic acid, HMD, MK-486
|
|---|---|---|---|
|
Severity of Hypotension During an Active Stand Test
|
96 mmHg
Standard Deviation 27
|
91 mmHg
Standard Deviation 28
|
96 mmHg
Standard Deviation 24
|
SECONDARY outcome
Timeframe: Up to 90 daysOutcome measures
| Measure |
Placebo
n=16 Participants
A placebo containing an inert substance, in capsule form that does not contain an active drug ingredient.
|
Low-Dose Carbidopa
n=16 Participants
300 mg/day
Other Names: Lodosyn ®, DL-α-methyl-α-hydrazino-3, 4-dihydroxyphenyl-propionic acid, HMD, MK-486
|
High-Dose Carbidopa
n=16 Participants
600 mg/day
Other Names: Lodosyn ®, DL-α-methyl-α-hydrazino-3, 4-dihydroxyphenyl-propionic acid, HMD, MK-486
|
|---|---|---|---|
|
Number of Participants Who Reported Worsening of OH Symptoms or Dropped Out Because of Worsening OH While on Active Study Drug
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to 90 DaysA tailored questionnaire to examine symptoms over the treatment period and the used of as needed medications. Each day will have a designated page. Since nausea/vomiting and hypertension occur together in FD we will use a diary consisting of a simplified version of the Rhodes Index 44 symptoms of nausea/retching, with items addressing vomiting/throwing up omitted, as most participants will have had anti-reflux surgery to prevent vomiting (fundoplication), graded on a 5-point scale (appendix 2). The diary will also include space to write down any adverse events on a daily basis.
Outcome measures
| Measure |
Placebo
n=16 Participants
A placebo containing an inert substance, in capsule form that does not contain an active drug ingredient.
|
Low-Dose Carbidopa
n=16 Participants
300 mg/day
Other Names: Lodosyn ®, DL-α-methyl-α-hydrazino-3, 4-dihydroxyphenyl-propionic acid, HMD, MK-486
|
High-Dose Carbidopa
n=16 Participants
600 mg/day
Other Names: Lodosyn ®, DL-α-methyl-α-hydrazino-3, 4-dihydroxyphenyl-propionic acid, HMD, MK-486
|
|---|---|---|---|
|
Frequency of Worsening Symptoms Noted in the Patient's Diary
|
0 symptoms
|
0 symptoms
|
0 symptoms
|
SECONDARY outcome
Timeframe: up to Week 14Norepinephrine concentration determined from a 24-hour urine sample in a bottle shielded from light containing preservative. Patients will be instructed to refrigerate their sample and bring it on the morning of their visit in a cool bag.
Outcome measures
| Measure |
Placebo
n=16 Participants
A placebo containing an inert substance, in capsule form that does not contain an active drug ingredient.
|
Low-Dose Carbidopa
n=16 Participants
300 mg/day
Other Names: Lodosyn ®, DL-α-methyl-α-hydrazino-3, 4-dihydroxyphenyl-propionic acid, HMD, MK-486
|
High-Dose Carbidopa
n=16 Participants
600 mg/day
Other Names: Lodosyn ®, DL-α-methyl-α-hydrazino-3, 4-dihydroxyphenyl-propionic acid, HMD, MK-486
|
|---|---|---|---|
|
24-h Urinary Norepinephrine Excretion
|
16 pg/mL
Standard Deviation 11
|
6 pg/mL
Standard Deviation 3
|
8 pg/mL
Standard Deviation 6
|
SECONDARY outcome
Timeframe: up to Week 14The measurement of blood pressure variability based on the standard deviation that also takes into account the underlying level of BP.
Outcome measures
| Measure |
Placebo
n=16 Participants
A placebo containing an inert substance, in capsule form that does not contain an active drug ingredient.
|
Low-Dose Carbidopa
n=16 Participants
300 mg/day
Other Names: Lodosyn ®, DL-α-methyl-α-hydrazino-3, 4-dihydroxyphenyl-propionic acid, HMD, MK-486
|
High-Dose Carbidopa
n=16 Participants
600 mg/day
Other Names: Lodosyn ®, DL-α-methyl-α-hydrazino-3, 4-dihydroxyphenyl-propionic acid, HMD, MK-486
|
|---|---|---|---|
|
Coefficient of Systolic BP Variability (Daytime)
|
19 mmHg
Standard Deviation 4
|
16 mmHg
Standard Deviation 4
|
15 mmHg
Standard Deviation 3
|
SECONDARY outcome
Timeframe: up to Week 14The morning surge will be calculated as the difference between the mean systolic blood pressure during the hour that included the lowest blood pressure during sleep and maximum value detected within 2-h of awakening from sleep
Outcome measures
| Measure |
Placebo
n=16 Participants
A placebo containing an inert substance, in capsule form that does not contain an active drug ingredient.
|
Low-Dose Carbidopa
n=16 Participants
300 mg/day
Other Names: Lodosyn ®, DL-α-methyl-α-hydrazino-3, 4-dihydroxyphenyl-propionic acid, HMD, MK-486
|
High-Dose Carbidopa
n=16 Participants
600 mg/day
Other Names: Lodosyn ®, DL-α-methyl-α-hydrazino-3, 4-dihydroxyphenyl-propionic acid, HMD, MK-486
|
|---|---|---|---|
|
Morning Surge in Systolic BP on Awakening From Sleep (24-h)
|
44 mmHg
Standard Deviation 24
|
19 mmHg
Standard Deviation 11
|
20 mmHg
Standard Deviation 9
|
Adverse Events
Low-Dose Carbidopa
Serious events: 1 serious events
Other events: 4 other events
Deaths: 1 deaths
High-Dose Carbidopa
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Low-Dose Carbidopa
n=16 participants at risk
300 mg/day
Other Name: Lodosyn ®, DL-α-methyl-α-hydrazino-3, 4-dihydroxyphenyl-propionic acid, HMD, MK-486
|
High-Dose Carbidopa
n=16 participants at risk
600 mg/day
Other Name: Lodosyn ®, DL-α-methyl-α-hydrazino-3, 4-dihydroxyphenyl-propionic acid, HMD, MK-486
|
Placebo
n=16 participants at risk
A placebo containing an inert substance, in capsule form that does not contain an active drug ingredient.
|
|---|---|---|---|
|
General disorders
Hospitaliztion
|
6.2%
1/16 • Number of events 1 • 1 year
|
0.00%
0/16 • 1 year
|
0.00%
0/16 • 1 year
|
Other adverse events
| Measure |
Low-Dose Carbidopa
n=16 participants at risk
300 mg/day
Other Name: Lodosyn ®, DL-α-methyl-α-hydrazino-3, 4-dihydroxyphenyl-propionic acid, HMD, MK-486
|
High-Dose Carbidopa
n=16 participants at risk
600 mg/day
Other Name: Lodosyn ®, DL-α-methyl-α-hydrazino-3, 4-dihydroxyphenyl-propionic acid, HMD, MK-486
|
Placebo
n=16 participants at risk
A placebo containing an inert substance, in capsule form that does not contain an active drug ingredient.
|
|---|---|---|---|
|
Gastrointestinal disorders
Diarrhea
|
25.0%
4/16 • 1 year
|
0.00%
0/16 • 1 year
|
0.00%
0/16 • 1 year
|
|
Vascular disorders
Syncope
|
0.00%
0/16 • 1 year
|
18.8%
3/16 • 1 year
|
0.00%
0/16 • 1 year
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place