Trial Outcomes & Findings for Evaluation of Safety and Tolerability of ENT-01 for the Treatment of Parkinson's Disease Related Constipation (NCT NCT03047629)
NCT ID: NCT03047629
Last Updated: 2023-12-27
Results Overview
Specific treatment related events of recurrent vomiting, recurrent diarrhea, abdominal pain, and hypotension will be assessed with respect to grade and frequency of occurrence.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
50 participants
Primary outcome timeframe
Through study completion, up to 11 weeks
Results posted on
2023-12-27
Participant Flow
50 subjects signed informed consent. 6 were screen failed during the run-in period and were not eligible to continue into the dose escalation period.
Participant milestones
| Measure |
Stage 1
Patients will begin with a dose level of 25 mg taken daily. Patients will dose escalated until they reach a maximum dose level of 200 mg daily or experience a dose limiting toxicity.
|
Stage 2: ENT-01
Patients will begin with a dose level of 75 mg taken daily. Patients will dose escalated until they reach a maximum dose level of 175 mg daily, experience a dose limiting toxicity or have a complete spontaneous bowel movement
|
Stage 2: Placebo Comparator
Patients randomized to receive placebo taken by mouth every day upon awakening
|
|---|---|---|---|
|
Overall Study
STARTED
|
10
|
26
|
8
|
|
Overall Study
COMPLETED
|
9
|
20
|
8
|
|
Overall Study
NOT COMPLETED
|
1
|
6
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Evaluation of Safety and Tolerability of ENT-01 for the Treatment of Parkinson's Disease Related Constipation
Baseline characteristics by cohort
| Measure |
Stage 1
n=10 Participants
Sentinel group to establish safe and tolerable dose of ENT-01
Patients will begin with a dose level of 25 mg taken daily. Patients will dose escalated until they reach a maximum dose level of 200 mg daily or experience a dose limiting toxicity.
|
ENT-01
n=26 Participants
ENT-01: Daily dosing with ENT-01.
Patients will begin with a dose level of 75 mg taken daily. Patients will dose escalated until they reach a maximum dose level of 175 mg daily, experience a dose limiting toxicity or have a complete spontaneous bowel movement
|
Placebo Comparator
n=8 Participants
Placebo to be taken by mouth every day upon awakening
Placebo: Daily dosing with a placebo
|
Total
n=44 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
65.5 years
STANDARD_DEVIATION 4.88 • n=5 Participants
|
72.6 years
STANDARD_DEVIATION 7.52 • n=7 Participants
|
73.1 years
STANDARD_DEVIATION 7.41 • n=5 Participants
|
70.4 years
STANDARD_DEVIATION 3 • n=4 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
14 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
30 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
9 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
42 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
10 participants
n=5 Participants
|
26 participants
n=7 Participants
|
8 participants
n=5 Participants
|
44 participants
n=4 Participants
|
|
Constipation Severity- Complete Spontaneous Bowel Movement per week
0-1 per week
|
4 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
26 Participants
n=4 Participants
|
|
Constipation Severity- Complete Spontaneous Bowel Movement per week
1.1-2 per week
|
4 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
13 Participants
n=4 Participants
|
|
Constipation Severity- Complete Spontaneous Bowel Movement per week
2.1-3 per week
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Through study completion, up to 11 weeksPopulation: Analysis completed as stage 1 and stage 2
Specific treatment related events of recurrent vomiting, recurrent diarrhea, abdominal pain, and hypotension will be assessed with respect to grade and frequency of occurrence.
Outcome measures
| Measure |
Stage 1
n=10 Participants
Sentinel group to establish safe and tolerable dose of ENT-01
Patients will begin with a dose level of 25 mg taken daily. Patients will dose escalated until they reach a maximum dose level of 200 mg daily or experience a dose limiting toxicity.
|
Stage 2: ENT-01
n=24 Participants
Patients will begin with a dose level of 75 mg taken daily. Patients will dose escalated until they reach a maximum dose level of 175 mg daily, experience a dose limiting toxicity or have a complete spontaneous bowel movement
|
Stage 2: Placebo Comparator
n=8 Participants
Placebo to be taken by mouth every day upon awakening
Placebo: Daily dosing with a placebo
|
|---|---|---|---|
|
Number of Participants With Treatment-related Adverse Events as Assessed by Common Terminology Criteria for Adverse Events.
|
9 Participants
|
16 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Through study completion, up to 11 weeksPopulation: Frequency of bowel movements was abondoned in protocol amendment date 01 Feb 2018.
The frequency of spontaneous bowel movements will be assessed at each dose across the study population and compared to baseline measures.
Outcome measures
Outcome data not reported
Adverse Events
Stage 1: ENT-01
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Stage 2: ENT-01
Serious events: 0 serious events
Other events: 26 other events
Deaths: 0 deaths
Stage 2: Placebo Comparator
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Stage 1: ENT-01
n=10 participants at risk
Sentinel group to establish safe and tolerable dose of ENT-01
Patients will begin with a dose level of 25 mg taken daily. Patients will dose escalated until they reach a maximum dose level of 200 mg daily or experience a dose limiting toxicity.
|
Stage 2: ENT-01
n=26 participants at risk
Patients will begin with a dose level of 75 mg taken daily. Patients will dose escalated until they reach a maximum dose level of 175 mg daily, experience a dose limiting toxicity or have a complete spontaneous bowel movement
|
Stage 2: Placebo Comparator
n=8 participants at risk
Placebo to be taken by mouth every day upon awakening
Placebo: Daily dosing with a placebo
|
|---|---|---|---|
|
Gastrointestinal disorders
Abdominal Distension
|
20.0%
2/10 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
0.00%
0/26 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
0.00%
0/8 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
|
Gastrointestinal disorders
Abdominal Pain
|
20.0%
2/10 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
11.5%
3/26 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
25.0%
2/8 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
|
Gastrointestinal disorders
Diarrhoea
|
40.0%
4/10 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
50.0%
13/26 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
25.0%
2/8 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
|
Gastrointestinal disorders
Flatulance
|
20.0%
2/10 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
3.8%
1/26 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
0.00%
0/8 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
|
Gastrointestinal disorders
Mucus Stools
|
10.0%
1/10 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
0.00%
0/26 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
0.00%
0/8 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
|
Gastrointestinal disorders
Nausea
|
40.0%
4/10 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
53.8%
14/26 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
37.5%
3/8 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
|
Gastrointestinal disorders
Vomiting
|
10.0%
1/10 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
7.7%
2/26 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
0.00%
0/8 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
|
Nervous system disorders
Dizziness
|
10.0%
1/10 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
19.2%
5/26 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
12.5%
1/8 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
|
Nervous system disorders
Headache
|
10.0%
1/10 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
7.7%
2/26 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
0.00%
0/8 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
|
Gastrointestinal disorders
Loss of Appetite
|
10.0%
1/10 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
0.00%
0/26 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
0.00%
0/8 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
|
Gastrointestinal disorders
Worsening Acid Reflux
|
0.00%
0/10 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
3.8%
1/26 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
12.5%
1/8 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
|
Gastrointestinal disorders
Worsening Hemmorrhoid
|
0.00%
0/10 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
0.00%
0/26 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
0.00%
0/8 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
|
Gastrointestinal disorders
Lower GI bleed
|
0.00%
0/10 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
3.8%
1/26 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
0.00%
0/8 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
|
Renal and urinary disorders
Blood in Urine
|
10.0%
1/10 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
0.00%
0/26 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
0.00%
0/8 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
|
Renal and urinary disorders
Urinary Retention
|
0.00%
0/10 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
0.00%
0/26 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
12.5%
1/8 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
|
Renal and urinary disorders
Urinary Tract Infection
|
0.00%
0/10 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
11.5%
3/26 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
0.00%
0/8 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
|
Renal and urinary disorders
Increased Urinary frequency
|
0.00%
0/10 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
7.7%
2/26 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
0.00%
0/8 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
|
Skin and subcutaneous tissue disorders
Skin lesions- rash
|
0.00%
0/10 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
11.5%
3/26 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
0.00%
0/8 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
|
Eye disorders
Eye Infection
|
0.00%
0/10 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
3.8%
1/26 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
0.00%
0/8 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
|
General disorders
Difficulty falling asleep
|
0.00%
0/10 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
3.8%
1/26 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
0.00%
0/8 • Adverse events were collected after the start of investigational product through the end of study visit, up to 11 weeks. Serious adverse events were to be reported within 30 days of last dose of study medication
NA. Adverse event collection does not differ from clinicaltrials.gov
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place