Subcutaneous Route and Pharmacology of Metoclopramide (SOPHA-Méto)

Subcutaneous (SC) route has become a standard of care of many drugs administration in palliative medicine. A preliminary study showed that, although it was widely adopted among palliative care practitioners for routinely prescribed medications, standards of proof are still lacking for many molecules. Among them, metoclopramide is a largely employed drug for nausea and vomiting treatment, particularly in palliative care and oncology. Therefore, the investigator aim to study absorption and efficacy of subcutaneous administration of metoclopramide.

Study Overview

• Status: Completed
• Conditions: Nausea; Vomiting
• Intervention / Treatment: Drug: metoclopramide intravenous

Detailed Description

In this cross-over study, each patient receives subcutaneous and intravenous metoclopramide, with a randomized order of administration. During each perfusion phases, metoclopramide is administrated with continuous flow, doses being increased every two days, first from 10 to 20 and then from 20 to 30 mg/d. In order to guarantee plasmatic balance during route change, the first dose of the second phase is extended for three days. Metoclopramide plasmatic concentration is measured at inclusion and at the end of each dose administration, with a total of 7 dosages.

Principal purpose of this research is to clarify subcutaneous bioavailability of metoclopramide. For this meaning, the mean difference between all subcutaneous and intravenous concentration ratios is compared. Secondary purposes consist of: calculating metoclopramide subcutaneous bioavailability for each study dose (10, 20 and 30 mg/d); describing dose-bioavailability relation for subcutaneous metoclopramide; comparing dose-concentration relationship of intravenous and subcutaneous metoclopramide; studying local tolerance by checking all inflammatory signs surrounding injection site; evaluating clinical efficacy by comparing between the two groups the number of vomiting episodes, use of Serotonin receptor antagonists and the nausea scores on a 11-level numerical scale.

Eighteen patients have to be analysed at least. For each patient not having completed the study, one more will be included in order to reach the eighteen necessary patients. Therefore, it is expected to include twenty-four patients. Included population characteristics will be described. A three-dimensional analysis with period, subject and dose is performed to determine metoclopramide absolute bioavailability. For secondary criteria, dose-concentration relation is analysed with a four-dimensional analysis; dose-bioavailability and dose-concentration relations are described by linear and log-linear regression. For principal purpose, only results of patients having completed the study are part of this aforementioned analyse.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Aquitaine
    • Bordeaux, Aquitaine, France, 33000
      • Centre Hospitalier Universitaire de Bordeaux - St André

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Man or woman > 18 years
• Patients hospitalized at the palliative medical care unit of University Hospital Bordeaux
• Patient whose life expectancy is greater to 4 weeks
• Patients suffering from nausea the day of inclusion with a greater than or equal score to 3/10 on a numerical scale (FR) from 0 to 10 and / or have had at least one vomiting within three days prior to inclusion
• Patients may be infused through an IV and subcutaneous (SC)
• Patient can communicate verbally or in writing
• Patients affiliates or beneficiaries of a social security fund
• Patient has given his written consent

Exclusion criteria

• Pregnant or breastfeeding women
• Current Treatment for severe and progressive threatening disease
• Treatment with oral or injectable metoclopramide within 3 days prior to inclusion
• Treatment with levodopa or dopamine agonists in progress
• Neuroleptic Processing
• Patient with lesion occlusive syndrome
• Patients at risk of gastrointestinal perforation
• Patient with clinical signs of gastrointestinal bleeding
• Parkinson's disease
• Patients with epilepsy not controlled by anti-seizure treatment
• Patients suffering from liver failure
• Patients with a heart rate less than 60 beats / min at baseline
• Patients with systolic blood pressure less than or equal to 90 mmHg at baseline
• History of allergy to metoclopramide
• History of allergy to ondansetron
• Previous history of tardive dyskinesia to neuroleptics or metoclopramide
• Previous history of pheochromocytoma
• Previous history of methemoglobinemia with metoclopramide
• History of deficit NADH-cytochrome b5 reductase
• Patient deprived of liberty by judicial or administrative decision
• Major protected by law
• Exclusion period Patient relative over another protocol.

Exclusion criteria

• Pregnant woman (blood β-HCG dosage ≥ 5 IU / L)
• Patients with a creatinine clearance less than or equal to 60 mL / min at baseline
• Patient with cardiac conduction disorders on ECG
• Patients with electrolyte imbalance in electrolytes

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: metoclopramide subcutaneous; every two days, first from 10 to 20 and then from 20 to 30 mg/d	Drug: metoclopramide intravenous; Administration route; Other Names: Primperan
Active Comparator: metoclopramide intravenous; first from 10 to 20 and then from 20 to 30 mg/d	Drug: metoclopramide intravenous; Administration route; Other Names: Primperan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute bioavailability of SubCutaneus administration metoclopramide	Calculated by the average ratio of plasma concentrations between SC route and IV on all doses of the study (10, 20 and 30 mg / d)	13 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute bioavailability of metoclopramide subcutaneously at each dose of the study (10, 20 and 30 mg / d)	Calculated by the ratio of plasma concentrations between SC route and the IV route;	13 days
Dose-bioavailability of metoclopramide for the SC route		13 days
Relations plasma concentration-dose metoclopramide subcutaneously and intravenously	Measured through their apparent clearances	13 days
Cutaneous inflammatory signs and subcutaneous at the puncture site		During 13 days
Numeric scale ranging from 0 to 10 for nausea		During 13 days
Number of vomiting in the dose level;		During 13 days

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux
• Investigators: Principal Investigator: Matthieu FRASCA, MD, University Hospital, Bordeaux

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2016
• Primary Completion (Actual): February 8, 2018
• Study Completion (Actual): February 8, 2019

Study Registration Dates

• First Submitted: May 29, 2015
• First Submitted That Met QC Criteria: June 8, 2015
• First Posted (Estimate): June 9, 2015

Study Record Updates

• Last Update Posted (Actual): March 7, 2019
• Last Update Submitted That Met QC Criteria: March 6, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: palliative care; metoclopramide; nausea; bioavailability; vomiting; pharmacology; subcutaneous route
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Nausea; Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Dopamine Agents; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Metoclopramide
• Other Study ID Numbers: CHUBX2014/10