Parkinson's DiseasePhase 1/2RASMETNCT03047629
Evaluation of Safety and Tolerability of ENT-01 for the Treatment of Parkinson's Disease Related Constipation
A Phase 1/2 study testing ENT-01 in people with Parkinson's Disease and Constipation, run by Enterin Inc. at 15 sites in United States.
Trial summary
This is a Phase 1/2a study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of an orally-administered medication to relieve symptoms of constipation associated with Parkinson's Disease. Ten patients will be enrolled in Phase 1, and will be studied over an 8-12 week period. Read more about this study
- Who is it for?
- Ages 30 to 86 years
- Conditions the study is for
- Parkinson's Disease, Constipation
- What is being tested?
- ENT-01
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 15 sitesUnited States
- Study dates
- 11 May 2017to 14 Jun 2018
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 86 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Parkinson's disease diagnosis confirmed by a neurologist specializing in movement disorders
- Insufficient criteria for a diagnosis of Irritable Bowel Syndrome
- Constipation for over 6 months, unresponsive to Milk of Magnesia, and requiring at least weekly treatment using an oral laxative, stool softener, bulking agent, and/or a suppository, and dissatisfaction with current treatment.
- Body Mass Index is 18-40 kg/m2
- At least 2 of the Rome IV functional constipation criteria are met
- Loose stools are rarely present without the use of laxatives
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- Patient is willing and able to sign informed consent and comply with all study procedures
- Patients must be able to read, understand, and accurately record data into the diary to guarantee full participation in the study
- Females only:
- Must have negative serum or urine pregnancy tests and must not be lactating
- If of child-bearing age: Must agree to using a hormonal (i.e., oral, implantable, or injectable) and either single- or double-barrier method of birth control throughout the study period. A vasectomized partner will be allowed as one in conjunction with another single-barrier method.
- If unable to have children: Must have this documented in the case report form (i.e., ubal ligation, hysterectomy, or post-menopausal [defined as a minimum of one year since last menstrual period]). Post-menopausal status will be confirmed by follicle stimulating hormone in women less than 60 years of age.
Who cannot join
- Unable or unwilling to provide informed consent or to comply with study procedures
- Diagnosis of secondary constipation beyond that of PD
- Structural or metabolic diseases that affect the GI system
- Functional GI disorder
- Unable or unwilling to withdraw from taking the following medications 2 weeks prior to the dose-escalation period and throughout the study: Laxatives, opiates, sedatives, hypnotics, anti-histamines, protein pump inhibitors or any medications which may cause constipation
- History of recent major surgery (within 60 days of screening)
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- Any clinically significant abnormalities on screening laboratories or physical examination as determined by the Investigator
- Neurological disorder other than PD
- On treatment with intra-jejunal dopamine
- Treatment with COMT inhibitors for fewer than 4 weeks (entacapone, tolcapone, Stalevo)
- Unable to maintain a stable diet regimen
- Patients with a cognitive impairment that preclude them from understanding the informed consent
- Patients placed under legal guardianship
- Acute GI illness within 48 hours of the baseline period
- History of major GI surgery (e.g. previous abdominal surgery, including cholecystectomy), except that patients with uncomplicated appendectomy are allowed
- ALT or AST > 1.5 X upper limit of normal (ULN) during screening
- Females who are pregnant or breastfeeding
- History of excessive alcohol use or substance abuse
- Patient or caregiver unable to administer daily oral dosing
- Participation in an investigational clinical study within the 6 months prior to dosing in the present study
- Any other reason, which in the opinion of the Investigator would confound proper interpretation of the study
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
United States15 sites
Parkinson's Disease and Movement Disorders Center of Boca Raton
Boca Raton, Florida, 33486
Riverhills Healthcare, Inc.
Cincinnati, Ohio, 45212
Parkinson's & Movement Disorders Center, UH Cleveland Medical Center
Cleveland, Ohio, 44106
Rocky Mountain Movement Disorders Center, PC
Englewood, Colorado, 80113
Quest Research Institute
Farmington Hills, Michigan, 48334
Penn State Health, Department of Neurology
Hershey, Pennsylvania, 17033
Neuroscience Research, University of Florida Jacksonville
Jacksonville, Florida, 32209
Keck Hospital of University of Southern California
Los Angeles, California, 90033
Movement Disorders Division, Mt. Sinai School of Medicine
New York, New York, 10029
Thomas Jefferson University, Department of Neurology
Philadelphia, Pennsylvania, 19107
MEDSOL Clinical Research
Port Charlotte, Florida, 33952
Sarasota Memory Hospital Clinical Research Ctr.
Sarasota, Florida, 34239
Suncoast Neuroscience Associates, Inc
St. Petersburg, Florida, 33713
USF Health Byrd Parkinson's Disease Movement Disorders Center of Excellence
Tampa, Florida, 33613
Georgetown Universtiy, Department of Neurology
Washington D.C., District of Columbia, 20007
About this study
Official title: A Multi-Center, Single-Dose, Multiple-Dose, Double-Blind, Placebo-Controlled Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Orally Administered ENT-01 for the Treatment of Parkinson's Disease Related Constipation
This is a Phase 1/2a study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of an orally-administered medication to relieve symptoms of constipation associated with Parkinson's Disease. Ten patients will be enrolled in Phase 1, and will be studied over an 8-12 week period. Forty patients will be enrolled in Phase 2, and will be studied over an 8-10 week period. All subjects will receive the study drug during one of the observational periods of the study.
Read the detailed description
Phase 1 will enroll 10 patients to assess the safety, tolerability, and pharmacokinetics of single escalating doses over a 30-60 day period. The dose-escalation period will be preceded by a 2-week run in period and followed by a 2-week wash-out period.
Phase 2 follow the safe completion of Phase 1. It will enroll 40 patients and is composed of 4 periods of study: 1) a 2-week run-in period, 2) a 3-5 week escalating dose period to identify a prokinetic dose in the initial set of 10 patients, 3) a 1-week period of randomized dosing (placebo versus the previously identified pro-kinetic dose), and 4) a 2-week wash-out period. Pharmacodynamics will be assessed along with safety and tolerability. Relative outcomes will be compared within each patient and across groups for the randomized dosing period.
Frequency of bowel movements and other non-motor symptoms of Parkinson's Disease will be collected over the course of both phases.
- Conditions
- Parkinson's Disease, Constipation
- Being tested
- ENT-01, Placebo
- Keywords
- non-motor symptoms
- Medical subject headings
- Parkinson Disease, Constipation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ENT-01Drug
Daily dosing with ENT-01. ENT-01 is an orally administered proprietary substance formulated as a small 25mg coated tablet. Dosing will range from 25-200mg, and the dose will be taken upon awakening on an empty stomach with 8oz water simultaneous to dopamine.
PlaceboOther
Daily dosing with a placebo
| Study group | Role | What they receive |
|---|---|---|
| ENT-01 | Experimental | ENT-01 at a to-be-determined dose taken by mouth every day upon awakening. Receives: Drug: ENT-01 |
| Placebo Comparator | Placebo comparator | Placebo to be taken by mouth every day upon awakening Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-related Adverse Events as Assessed by Common Terminology Criteria for Adverse Events.
Specific treatment related events of recurrent vomiting, recurrent diarrhea, abdominal pain, and hypotension will be assessed with respect to grade and frequency of occurrence.
Measured: Through study completion, up to 11 weeks
Secondary outcomes (1)
Frequency of Bowel Movements
The frequency of spontaneous bowel movements will be assessed at each dose across the study population and compared to baseline measures.
Measured: Through study completion, up to 11 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2017 (estimated)
- Study start11 May 2017
- Primary completion25 Apr 2018
- Study completion14 Jun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Parkinson's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- Phase 1 is a single group; Phase 2 will begin subsequent to the safe completion of Phase 1. Phase 2 patients will undergo randomization for parallel study during one period of observation of the course of the study phase.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Enterin Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Denise Barbut, MD FRCP, Study chair, Enterin Inc.Steven Frucht, MD, Principal investigator, NYU Langone HealthRobert Hauser, MD MBA, Principal investigator, University of South Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03047629
- Sponsor's protocol ID
- ENT-01
- Acronym
- RASMET
- Status last verified
- Dec 2023
- First submitted
- 3 Feb 2017
- Last updated
- 27 Dec 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Anonymized data may be shared with other clinical researchers outside of this study that are involved in similar research at non-participating institutions.
Publications
Hauser RA, Sutherland D, Madrid JA, Rol MA, Frucht S, Isaacson S, Pagan F, Maddux BN, Li G, Tse W, Walter BL, Kumar R, Kremens D, Lew MF, Ellenbogen A, Oguh O, Vasquez A, Kinney W, Lowery M, Resnick M, Huff N, Posner J, Ballman KV, Harvey BE, Camilleri M, Zasloff M, Barbut D. Targeting neurons in the gastrointestinal tract to treat Parkinson's disease. Clin Park Relat Disord. 2019 Jul 2;1:2-7. doi: 10.1016/j.prdoa.2019.06.001. eCollection 2019.
PubMed 34316590
Study at a glance
From the registry record, last updated by the sponsor on 27 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-Center, Single-Dose, Multiple-Dose, Double-Blind, Placebo-Controlled Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Orally Administered ENT-01 for the Treatment of Parkinson's Disease Related Constipation
- ClinicalTrials.gov ID
- NCT03047629
- Acronym / sponsor ID
- RASMET / ENT-01
- Conditions
- Parkinson's Disease, Constipation
- Keywords
- non-motor symptoms
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Enterin Inc.Industry (pharma, biotech, devices)
- Study start
- 11 May 2017 (actual)
- Primary completion
- 25 Apr 2018 (actual)
- Study completion
- 14 Jun 2018 (actual)
- First posted
- 9 Feb 2017 (estimated)
- Results
- Posted 30 Nov 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 1/2a study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of an orally-administered medication to relieve symptoms of constipation associated with Parkinson's Disease. Ten patients will be enrolled in Phase 1, and will be studied over an 8-12 week period. Forty patients will be enrolled in Phase 2, and will be studied over an 8-10 week period. All subjects will receive the study drug during one of the observational periods of the study.
Detailed description
Phase 1 will enroll 10 patients to assess the safety, tolerability, and pharmacokinetics of single escalating doses over a 30-60 day period. The dose-escalation period will be preceded by a 2-week run in period and followed by a 2-week wash-out period.
Phase 2 follow the safe completion of Phase 1. It will enroll 40 patients and is composed of 4 periods of study: 1) a 2-week run-in period, 2) a 3-5 week escalating dose period to identify a prokinetic dose in the initial set of 10 patients, 3) a 1-week period of randomized dosing (placebo versus the previously identified pro-kinetic dose), and 4) a 2-week wash-out period. Pharmacodynamics will be assessed along with safety and tolerability. Relative outcomes will be compared within each patient and across groups for the randomized dosing period.
Frequency of bowel movements and other non-motor symptoms of Parkinson's Disease will be collected over the course of both phases.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Phase 1 is a single group; Phase 2 will begin subsequent to the safe completion of Phase 1. Phase 2 patients will undergo randomization for parallel study during one period of observation of the course of the study phase.
| Arm | Type | Receives |
|---|---|---|
| ENT-01 | Experimental | Drug: ENT-01ENT-01 at a to-be-determined dose taken by mouth every day upon awakening. |
| Placebo Comparator | Placebo comparator | Other: PlaceboPlacebo to be taken by mouth every day upon awakening |
Who may qualify
- Ages
- 30 to 86 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Parkinson's disease diagnosis confirmed by a neurologist specializing in movement disorders
- Insufficient criteria for a diagnosis of Irritable Bowel Syndrome
- Constipation for over 6 months, unresponsive to Milk of Magnesia, and requiring at least weekly treatment using an oral laxative, stool softener, bulking agent, and/or a suppository, and dissatisfaction with current treatment.
- Body Mass Index is 18-40 kg/m2
- At least 2 of the Rome IV functional constipation criteria are met
Key exclusion criteria (21 listed)
- Unable or unwilling to provide informed consent or to comply with study procedures
- Diagnosis of secondary constipation beyond that of PD
- Structural or metabolic diseases that affect the GI system
- Functional GI disorder
- Unable or unwilling to withdraw from taking the following medications 2 weeks prior to the dose-escalation period and throughout the study: Laxatives, opiates, sedatives, hypnotics, anti-histamines, protein pump inhibitors or any medications which may cause constipation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ENT-01Daily dosing with ENT-01. ENT-01 is an orally administered proprietary substance formulated as a small 25mg coated tablet. Dosing will range from 25-200mg, and the dose will be taken upon awakening on an empty stomach with 8oz water simultaneous to dopamine. | Drug | ENT-01 |
| PlaceboDaily dosing with a placebo | Other | Placebo Comparator |
Primary outcome
Number of Participants With Treatment-related Adverse Events as Assessed by Common Terminology Criteria for Adverse Events.
Time frame: Through study completion, up to 11 weeks
Specific treatment related events of recurrent vomiting, recurrent diarrhea, abdominal pain, and hypotension will be assessed with respect to grade and frequency of occurrence.
1 secondary outcome
Frequency of Bowel Movements
Time frame: Through study completion, up to 11 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Dec 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 34316590Hauser RA, Sutherland D, Madrid JA, Rol MA, Frucht S, Isaacson S, Pagan F, Maddux BN, Li G, Tse W, Walter BL, Kumar R, Kremens D, Lew MF, Ellenbogen A, Oguh O, Vasquez A, Kinney W, Lowery M, Resnick M, Huff N, Posner J, Ballman KV, Harvey BE, Camilleri M, Zasloff M, Barbut D. Targeting neurons in the gastrointestinal tract to treat Parkinson's disease. Clin Park Relat Disord. 2019 Jul 2;1:2-7. doi: 10.1016/j.prdoa.2019.06.001. eCollection 2019.
- Individual participant dataSharing planned: No. Anonymized data may be shared with other clinical researchers outside of this study that are involved in similar research at non-participating institutions.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Denise Barbut, MD FRCP study chair
Enterin Inc.
Steven Frucht, MD principal investigator
NYU Langone Health
Robert Hauser, MD MBA principal investigator
University of South Florida
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ENT-01 in people with Parkinson's Disease and Constipation, run by Enterin Inc. at 15 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Nov 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment-related Adverse Events as Assessed by Common Terminology Criteria for Adverse Events. (time frame: Through study completion, up to 11 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03047629, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Dec 2023.