A Study of the Safety and Efficacy of Combination Therapy With Morphine, Phenylephrine and Sorbitol in Human Subjects

Study Overview
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Brief Summary
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Efficacy and Safety of the combined oral adjuvants phenylephrine and sorbitol on oral low dose morphine analgesia.

Detailed Description
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The primary objective of this study is to determine the efficacy of the combined oral adjuvants phenylephrine and sorbitol on oral low dose morphine analgesia.

Official Title
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A Randomized, Double-Blind, Single-Center, 5 Way Cross-Over Study to Assess the Effect of Adding Oral Phenylephrine and Oral Sorbitol to Low Dose (1.5 mg) Plain Oral Morphine in Human Volunteers: Analgesia and Side Effect Assessment.

Conditions
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Acute Pain

Intervention / Treatment
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* Drug: Morphine
* Drug: Morphine
* Drug: Sorbitol+Phenylephrine
* Drug: Sorbitol+Phenylephrine+Morphine
* Drug: Sorbitol low concentration+Phenylephrine+Morphine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to provide written informed consent Healthy male or female between 18 and 40 years of age, inclusive. Women have to test negative for pregnancy. Body weight within 15% of ideal body weight based on Metropolitan Life assurance tables. No concomitant medications (prescription, OTC, vitamins, dietary supplements) within 7 days prior to administration of study medication and during the study period. Ability to adhere to the visit schedule and protocol requirements and be available to complete the study Ability to participate successfully in training sessions that will be arranged for the volunteers prior to the study day, during which they will acquire consistency in the tests to be performed. Ability to satisfy a medical examiner about fitness to participate in the study Exclusion Criteria: prior use of chronic opioids mental illness prior or present evidence of significant concomitant disease, including renal, hepatic, cardiovascular, pulmonary, endocrinological, hematopoietic, or gastrointestinal disease, a neoplasm or any other clinically significant medical disorder, which in the Investigator's judgment contraindicate administration of the study medications known allergy to any of the drugs used in this study history of drug or alcohol abuse significant abnormalities in screening physical exam administration of drugs that may potentially inhibit or induce liver cytochrome P450 activity within 3 weeks prior to Day 0 any acute medical situation (e.g. acute infection) within 48 hours of Day 0, which is considered of significance by the Principal Investigator unusual diet administration of experimental medications within the previous 12 weeks. inability to communicate well with the Investigator (i.e., language problem, poor mental development or impaired cerebral function) subjects who, in the judgment of the investigators, are likely to be non-compliant or uncooperative or unwilling to sign a consent form

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Morphine High Dose | Drug: Morphine<br>* Morphine<br>|
| Placebo Comparator: 2<br>Morphine Low Dose | Drug: Morphine<br>* Morphine low dose<br>|
| Placebo Comparator: 3<br>Sorbitol Phenylephrine | Drug: Sorbitol+Phenylephrine<br>* Sorbitol+Phenylephrine<br>|
| Experimental: 4<br>Sorbitol high concentration+Phenylephrine+Morphine | Drug: Sorbitol+Phenylephrine+Morphine<br>* Sorbitol+Phenylephrine+Morphine<br>|
| Experimental: 5<br>Sorbitol low concentration+Phenylephrine+Morphine | Drug: Sorbitol low concentration+Phenylephrine+Morphine<br>* Sorbitol low concentration+Phenylephrine+Morphine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety |  | 8 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy |  | 4 hours |