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

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.

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

Study Overview

• Status: Completed
• Conditions: Acute Pain
• Intervention / Treatment: Drug: Morphine; Drug: Morphine; Drug: Sorbitol+Phenylephrine; Drug: Sorbitol+Phenylephrine+Morphine; Drug: Sorbitol low concentration+Phenylephrine+Morphine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Israel
  • Jerusalem, Israel, 91120
    • Hadassah Hebrew University Medical Center, Department of Anesthesiology
  • Jerusalem, Israel
    • Hadassah En Kerem Medical Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: 1; Morphine High Dose	Drug: Morphine; Morphine; Drug: Morphine; Morphine low dose
PLACEBO_COMPARATOR: 2; Morphine Low Dose	Drug: Morphine; Morphine; Drug: Morphine; Morphine low dose
PLACEBO_COMPARATOR: 3; Sorbitol Phenylephrine	Drug: Sorbitol+Phenylephrine; Sorbitol+Phenylephrine
EXPERIMENTAL: 4; Sorbitol high concentration+Phenylephrine+Morphine	Drug: Sorbitol+Phenylephrine+Morphine; Sorbitol+Phenylephrine+Morphine
EXPERIMENTAL: 5; Sorbitol low concentration+Phenylephrine+Morphine	Drug: Sorbitol low concentration+Phenylephrine+Morphine; Sorbitol low concentration+Phenylephrine+Morphine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety	8 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Efficacy	4 hours

Collaborators and Investigators

• Sponsor: BioLineRx, Ltd.
• Investigators: Principal Investigator: Yehuda Ginosar, Bsc, MBBS, Department of Anesthesiology, Hadassah Hebrew University Medical Center

Study record dates

Study Major Dates

• Study Start: September 1, 2006
• Primary Completion (ACTUAL): June 1, 2007
• Study Completion (ACTUAL): August 1, 2007

Study Registration Dates

• First Submitted: September 11, 2006
• First Submitted That Met QC Criteria: September 11, 2006
• First Posted (ESTIMATE): September 12, 2006

Study Record Updates

• Last Update Posted (ESTIMATE): April 15, 2008
• Last Update Submitted That Met QC Criteria: April 14, 2008
• Last Verified: April 1, 2008

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Acute Pain; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Gastrointestinal Agents; Protective Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Cardiotonic Agents; Analgesics, Opioid; Narcotics; Respiratory System Agents; Cathartics; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Nasal Decongestants; Adrenergic alpha-1 Receptor Agonists; Morphine; Sorbitol; Phenylephrine; Oxymetazoline
• Other Study ID Numbers: BL-3010