Constipation Drug InducedPhase 1NCT02737059
Effect of Naloxegol on Gastric, Small Bowel, and Colonic Transit in Healthy Subjects
A Phase 1 study testing Naloxegol and Codeine in people with Constipation Drug Induced, run by Michael Camilleri at 1 site in United States.
Trial summary
This research study was being done to study the effect of codeine and Naloxegol for 3 days compared to placebo on the movement of food through the colon of healthy individuals. Codeine is a commonly used pain-relieving drug that often causes constipation as an unwanted side effect. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Constipation Drug Induced
- What is being tested?
- Naloxegol and Codeine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 72 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jul 2016to 10 May 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Body Mass Index (BMI) between 19 and 30 kg/m^2 and absolute weight between 45 and 100 kg. for both males and females.
- Females who are non-pregnant, non-lactating, postmenopausal for at least one year (as evidenced by last menses 12 months from Day 0), surgically sterile, or willing to use a clinically-approved method of contraception from 35 days prior to Day 0 until 30 days after the last dose of study medication
- Males who are surgically sterile or willing to use a clinically approved method of contraception from Day 0 until 30 days after the last dose of study medication.
- Absence of gastrointestinal symptoms unless deemed not clinically significant by the Investigator.
- Able to understand and willing to sign informed consent
- Negative urine drug screen at screening
Who cannot join
- Structural or metabolic diseases/conditions that affect the gastrointestinal system, or functional gastrointestinal disorders. For screening, three or more "YES" responses on the Bowel Disease Questionnaire will be used to exclude subjects with irritable bowel syndrome.
- Use of drugs or agents within the past 2 weeks or planned use in the subsequent 4 weeks during the study period that: Alter GI transit including laxatives, magnesium or aluminum-containing antacids, prokinetic, erythromycin, narcotics, anticholinergics, tricyclic antidepressants, Selective serotonin re-uptake inhibitors (SSRI) and newer antidepressants.
- Analgesic drugs including opiates, NSAID, cyclooxygenase-2 (COX 2) inhibitors
- Use of non-prescription or prescription medications within 7 days or within five half-lives prior to Day 0 for that particular medication. Note: Low stable doses of thyroid replacement, estrogen replacement, and birth control pills or depot injections, and use of acetaminophen on as needed basis are permissible.
- A score of greater than or equal to 11 for either score obtained from the Hospital Anxiety Depression Scale
- Positive urine drug screen at screening
Show all 17Show fewer
- Female subjects who are pregnant or breast feeding.
- Clinical evidence (including physical exam, previous laboratory tests) or significant cardiovascular, respiratory, renal, hepatic, gastrointestinal, hematological, neurological, psychiatric, or other disease that interfere with the objectives of the study. Patients with previously high transaminase levels (AST, ALT) may be retested and if the results are less than 1.5 times the upper limit of normal will be included as long as they do not have an underlying known liver disease.
- Symptoms of a significant clinical illness in the preceding two weeks.
- Participation in another clinical study within the past 30 days.
- Subjects known allergy or hypersensitive to multiple drug compounds (greater than or equal to 3 drug compounds), naloxegol or opioid antagonists, codeine sulfate, eggs or any components of the study medication
- Daily use of any tobacco products within 6 months prior to Day 0
- Previous exposure to naloxegol
- Any other conditions or prior therapy which, in the opinion of the Investigator, would make the subject unsuitable for this study
- Contraindications to use of naloxegol in accordance with FDA guidance: suspected GI obstruction or at increased risk of recurrent obstruction; concomitant use of strong CYP3A4 inhibitors such as clarithromycin and ketoconazole
- Concomitant treatment with moderate CYP3A4 inhibitors (diltiazem, erythromycin, verapamil) or strong CYP3A4 inducers (rifampin) or other opioid antagonists.
- History of substance abuse.
Trial locations and contacts
1 site in 1 country.
United States1 site
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
About this study
Official title: A Phase I Randomized, Double-Blinded, Placebo-Controlled Study of the Effect of Naloxegol on Gastric, Small Bowel, and Colonic Transit in Healthy Subjects
This research study was being done to study the effect of codeine and Naloxegol for 3 days compared to placebo on the movement of food through the colon of healthy individuals. Codeine is a commonly used pain-relieving drug that often causes constipation as an unwanted side effect. Naloxegol is a medication recently approved by the FDA for treatment of constipation induced by Codeine.
The hypothesis for this study was that Naloxegol reduces the retardation of small bowel and colonic transit induced by codeine in healthy participants.
Read the detailed description
This was a single center, randomized, double-blind, placebo-controlled, parallel-group, Phase I study of the effects of naloxegol, a novel mu-opioid antagonist, on gastrointestinal and colonic transit in the presence or absence of the mu-opiate, codeine. There is a need to develop effective medications for the treatment of opiate-induced constipation and other motility disorders. Currently available opiates are complicated by addictive potential and induction of troublesome constipation.
- Conditions
- Constipation Drug Induced
- Being tested
- Naloxegol, Codeine, codeine placebo, naloxegol placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NaloxegolDrug
Also called MOVANTIK
25mg daily
CodeineDrug
30mg 4 times daily
codeine placeboDrug
4 times daily (placebo will be made to match the codeine)
naloxegol placeboDrug
placebo will match naloxegol, given daily
| Study group | Role | What they receive |
|---|---|---|
| Codeine/naloxegol placebo | Placebo comparator | Each subject will receive two medications to which they are randomized for 1 day before and for the 2 days during transit measurement.
Codeine tablet 30 mg q.i.d., and placebo tablet matching naloxegol q.d. Receives: Drug: Codeine; Drug: naloxegol placebo |
| Naloxegol/ codeine placebo | Placebo comparator | Each subject will receive two medications to which they are randomized for 1 day before and for the 2 days during transit measurement.
Naloxegol tablet 25 mg q.d and placebo tablet matching codeine q.i.d. Receives: Drug: Naloxegol; Drug: codeine placebo |
| Codeine/ naloxegol | Active comparator | Each subject will receive two medications to which they are randomized for 1 day before and for the 2 days during transit measurement.
Codeine tablet 30 mg q.i.d., and naloxegol tablet 25 mg q.d. Receives: Drug: Naloxegol; Drug: Codeine |
| codeine placebo/ naloxegol placebo | Active comparator | Each subject will receive two medications to which they are randomized for 1 day before and for the 2 days during transit measurement.
Placebo tablet matching codeine q.i.d., and placebo tablet matching naloxegol q.d. Receives: Drug: codeine placebo; Drug: naloxegol placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Gastric emptying (t1/2)
The time for half of the ingested solids or liquids to leave the stomach.
Measured: Day 2
Colonic filling (%) at 6 hours
Percent of the radio-labeled meal that reached the colon at 6 hours, indirectly reflecting small bowel transit time.
Measured: Day 2 (6 hours)
Colonic geometric center (GC) at 24 hours
The scintigraphic method is used to measure colonic transit. An isotope is adsorbed on activated charcoal particles and delivered to the colon in a delayed release capsule. Anterior and posterior gamma images are taken hourly. The geometric center (GC) is the weighted average of counts in the different colonic regions. The scale ranges from 1 to 5; a high GC implies faster colonic transit, a GC of 1 implies all isotope is in the ascending colon, and a GC of 5 implies all isotope is in the stool.
Measured: Day 2 ( 24 hours)
Secondary outcomes (2)
Colonic transit summarized by GC at 48 hours hours hours colonic transit summarized by GC at 4 and 48 hours Colonic transit at 4 and 48 hours
The scintigraphic method is used to measure colonic transit. An isotope is adsorbed on activated charcoal particles and delivered to the colon in a delayed release capsule. Anterior and posterior gamma images are taken hourly. The geometric center (GC) is the weighted average of counts in the different colonic regions. The scale ranges from 1 to 5; a high GC implies faster colonic transit, a GC of 1 implies all isotope is in the ascending colon, and a GC of 5 implies all isotope is in the stool.
Measured: Day 2 (48 hours)
Ascending Colon Emptying (ACE) T1/2
Ascending colon emptying half-time will be estimated by power exponential analysis of the proportionate emptying over time of counts from the colon.
Measured: Day 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2016 (estimated)
- Study start1 Jul 2016
- Primary completion10 May 2017
- Study completion10 May 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Constipation Drug InducedStudies 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- Michael Camilleri
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor-investigator, Michael Camilleri, Mayo Clinic
- Investigators
- Michael Camilleri, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02737059
- Sponsor's protocol ID
- 15-007863
- Other IDs
- UL1TR000135
- Status last verified
- Aug 2017
- First submitted
- 8 Apr 2016
- Last updated
- 30 Aug 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Randomized, Double-Blinded, Placebo-Controlled Study of the Effect of Naloxegol on Gastric, Small Bowel, and Colonic Transit in Healthy Subjects
- ClinicalTrials.gov ID
- NCT02737059
- Acronym / sponsor ID
- 15-007863
- Conditions
- Constipation Drug Induced
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- Michael CamilleriUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- 1 Jul 2016 (actual)
- Primary completion
- 10 May 2017 (actual)
- Study completion
- 10 May 2017 (actual)
- First posted
- 13 Apr 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research study was being done to study the effect of codeine and Naloxegol for 3 days compared to placebo on the movement of food through the colon of healthy individuals. Codeine is a commonly used pain-relieving drug that often causes constipation as an unwanted side effect. Naloxegol is a medication recently approved by the FDA for treatment of constipation induced by Codeine.
The hypothesis for this study was that Naloxegol reduces the retardation of small bowel and colonic transit induced by codeine in healthy participants.
Detailed description
This was a single center, randomized, double-blind, placebo-controlled, parallel-group, Phase I study of the effects of naloxegol, a novel mu-opioid antagonist, on gastrointestinal and colonic transit in the presence or absence of the mu-opiate, codeine. There is a need to develop effective medications for the treatment of opiate-induced constipation and other motility disorders. Currently available opiates are complicated by addictive potential and induction of troublesome constipation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Codeine/naloxegol placebo | Placebo comparator | Drug: Codeine, Drug: naloxegol placeboEach subject will receive two medications to which they are randomized for 1 day before and for the 2 days during transit measurement. Codeine tablet 30 mg q.i.d., and placebo tablet matching naloxegol q.d. |
| Naloxegol/ codeine placebo | Placebo comparator | Drug: Naloxegol, Drug: codeine placeboEach subject will receive two medications to which they are randomized for 1 day before and for the 2 days during transit measurement. Naloxegol tablet 25 mg q.d and placebo tablet matching codeine q.i.d. |
| Codeine/ naloxegol | Active comparator | Drug: Naloxegol, Drug: CodeineEach subject will receive two medications to which they are randomized for 1 day before and for the 2 days during transit measurement. Codeine tablet 30 mg q.i.d., and naloxegol tablet 25 mg q.d. |
| codeine placebo/ naloxegol placebo | Active comparator | Drug: codeine placebo, Drug: naloxegol placeboEach subject will receive two medications to which they are randomized for 1 day before and for the 2 days during transit measurement. Placebo tablet matching codeine q.i.d., and placebo tablet matching naloxegol q.d. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Body Mass Index (BMI) between 19 and 30 kg/m^2 and absolute weight between 45 and 100 kg. for both males and females.
- Females who are non-pregnant, non-lactating, postmenopausal for at least one year (as evidenced by last menses 12 months from Day 0), surgically sterile, or willing to use a clinically-approved method of contraception from 35 days prior to Day 0 until 30 days after the last dose of study medication
- Males who are surgically sterile or willing to use a clinically approved method of contraception from Day 0 until 30 days after the last dose of study medication.
- Absence of gastrointestinal symptoms unless deemed not clinically significant by the Investigator.
- Able to understand and willing to sign informed consent
Key exclusion criteria (17 listed)
- Structural or metabolic diseases/conditions that affect the gastrointestinal system, or functional gastrointestinal disorders. For screening, three or more "YES" responses on the Bowel Disease Questionnaire will be used to exclude subjects with irritable bowel syndrome.
- Use of drugs or agents within the past 2 weeks or planned use in the subsequent 4 weeks during the study period that: Alter GI transit including laxatives, magnesium or aluminum-containing antacids, prokinetic, erythromycin, narcotics, anticholinergics, tricyclic antidepressants, Selective serotonin re-uptake inhibitors (SSRI) and newer antidepressants.
- Analgesic drugs including opiates, NSAID, cyclooxygenase-2 (COX 2) inhibitors
- Use of non-prescription or prescription medications within 7 days or within five half-lives prior to Day 0 for that particular medication. Note: Low stable doses of thyroid replacement, estrogen replacement, and birth control pills or depot injections, and use of acetaminophen on as needed basis are permissible.
- A score of greater than or equal to 11 for either score obtained from the Hospital Anxiety Depression Scale
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 |
|---|---|---|
| NaloxegolAlso: MOVANTIK25mg daily | Drug | Codeine/ naloxegol, Naloxegol/ codeine placebo |
| Codeine30mg 4 times daily | Drug | Codeine/ naloxegol, Codeine/naloxegol placebo |
| codeine placebo4 times daily (placebo will be made to match the codeine) | Drug | Naloxegol/ codeine placebo, codeine placebo/ naloxegol placebo |
| naloxegol placeboplacebo will match naloxegol, given daily | Drug | Codeine/naloxegol placebo, codeine placebo/ naloxegol placebo |
Primary outcome
Gastric emptying (t1/2)
Time frame: Day 2
The time for half of the ingested solids or liquids to leave the stomach.
Colonic filling (%) at 6 hours
Time frame: Day 2 (6 hours)
Percent of the radio-labeled meal that reached the colon at 6 hours, indirectly reflecting small bowel transit time.
Colonic geometric center (GC) at 24 hours
Time frame: Day 2 ( 24 hours)
The scintigraphic method is used to measure colonic transit. An isotope is adsorbed on activated charcoal particles and delivered to the colon in a delayed release capsule. Anterior and posterior gamma images are taken hourly. The geometric center (GC) is the weighted average of counts in the different colonic regions. The scale ranges from 1 to 5; a high GC implies faster colonic transit, a GC of 1 implies all isotope is in the ascending colon, and a GC of 5 implies all isotope is in the stool.
2 secondary outcomes
Colonic transit summarized by GC at 48 hours hours hours colonic transit summarized by GC at 4 and 48 hours Colonic transit at 4 and 48 hours
Time frame: Day 2 (48 hours)
Ascending Colon Emptying (ACE) T1/2
Time frame: Day 2
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Aug 2017.
- Individual participant dataSharing planned: No
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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.
Michael Camilleri, MD principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Naloxegol and Codeine in people with Constipation Drug Induced, run by Michael Camilleri at 1 site 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 6 inclusion and 17 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 30 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Gastric emptying (t1/2) (time frame: Day 2). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Aug 2017.