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This is a healthy volunteer three-way crossover study. A total of 12 subjects will receive three single administrations of 1 g rectal suppositories (containing either 5 mg NRL001, 10 mg NRL001 or matching placebo), with a washout period of at least 7 days between dosings. A further 12 subjects will receive three single administrations of 2 g rectal suppositories (containing either 5 mg NRL001, 10 mg NRL001 or matching placebo), again with a 7 day washout period between dosings. The pharmacodynamic response, pharmacokinetics and safety profile will be determined.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 g suppository | Experimental | Subjects receive 5 mg NRL001, 10 mg NRL001 and placebo in a 1g rectal suppository |
|
| 2 g suppository | Experimental | Subjects receive 5 mg NRL001, 10 mg NRL001 and placebo in a 2 g rectal suppository. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| NRL001 | Drug | Subjects receive single doses of 5 mg NRL001, 10 mg NRL001 and placebo in a 1 g rectal suppository, with a 7-day washout period between dosing. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in MARP after a single dose | 6 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetic plasma assessment to determine systemic uptake | 6 hours | |
| Adverse events | 6 hours | |
| Cardiovascular parameters; heart rate and blood pressure |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Hans-Jürgen Gruss, MD | Norgine | Study Director |
| John H Scholefield, MD | Nottingham University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of GI Surgery, Nottingham University Hospital | Nottingham | NG7 2UH | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24499492 | Derived | Simpson JA, Bush D, Gruss HJ, Jacobs A, Pediconi C, Scholefield JH. A randomised, controlled, crossover study to investigate the safety and response of 1R,2S-methoxamine hydrochloride (NRL001) on anal function in healthy volunteers. Colorectal Dis. 2014 Mar;16 Suppl 1:5-15. doi: 10.1111/codi.12541. |
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| ID | Term |
|---|---|
| D005242 | Fecal Incontinence |
| ID | Term |
|---|---|
| D012002 | Rectal Diseases |
| D007410 | Intestinal Diseases |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
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| NRL001 | Drug | Subjects receive single doses of 5 mg NRL001, 10 mg NRL001 and placebo in a 2 g rectal suppository, with a 7-day washout period between dosing. |
|
| 6 hours |