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Subcutaneous Route and Pharmacology of Metoclopramide (SOPHA-Méto)

Primary Purpose

Nausea, Vomiting

Status

Completed

Phase

Phase 3

Locations

France

Study Type

Interventional

Intervention

metoclopramide intravenous

About this trial

This is an interventional treatment trial for Nausea focused on measuring metoclopramide, subcutaneous route, palliative care, pharmacology, bioavailability, nausea, vomiting

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Centre Hospitalier Universitaire de Bordeaux - St André

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

metoclopramide subcutaneous

metoclopramide intravenous

Arm Description

every two days, first from 10 to 20 and then from 20 to 30 mg/d

first from 10 to 20 and then from 20 to 30 mg/d

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

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;

Dose-bioavailability of metoclopramide for the SC route

Relations plasma concentration-dose metoclopramide subcutaneously and intravenously

Measured through their apparent clearances

Cutaneous inflammatory signs and subcutaneous at the puncture site

Numeric scale ranging from 0 to 10 for nausea

Number of vomiting in the dose level;

Full Information

NCT ID

NCT02466984

First Posted

May 29, 2015

Last Updated

March 6, 2019

Sponsor

University Hospital, Bordeaux

1. Study Identification

Unique Protocol Identification Number

NCT02466984

Brief Title

Subcutaneous Route and Pharmacology of Metoclopramide

Acronym

SOPHA-Méto

Official Title

Subcutaneous Route and Pharmacology of Metoclopramide

Study Type

Interventional

2. Study Status

Record Verification Date

March 2019

Overall Recruitment Status

Completed

Study Start Date

July 2016 (Actual)

Primary Completion Date

February 8, 2018 (Actual)

Study Completion Date

February 8, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Hospital, Bordeaux

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Nausea, Vomiting

Keywords

metoclopramide, subcutaneous route, palliative care, pharmacology, bioavailability, nausea, vomiting

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

5 (Actual)

8. Arms, Groups, and Interventions

Arm Title

metoclopramide subcutaneous

Arm Type

Experimental

Arm Description

every two days, first from 10 to 20 and then from 20 to 30 mg/d

Arm Title

metoclopramide intravenous

Arm Type

Active Comparator

Arm Description

first from 10 to 20 and then from 20 to 30 mg/d

Intervention Type

Drug

Intervention Name(s)

metoclopramide intravenous

Other Intervention Name(s)

Primperan

Intervention Description

Administration route

Primary Outcome Measure Information:

Title

Absolute bioavailability of SubCutaneus administration metoclopramide

Description

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)

Time Frame

13 days

Secondary Outcome Measure Information:

Title

Absolute bioavailability of metoclopramide subcutaneously at each dose of the study (10, 20 and 30 mg / d)

Description

Calculated by the ratio of plasma concentrations between SC route and the IV route;

Time Frame

13 days

Title

Dose-bioavailability of metoclopramide for the SC route

Time Frame

13 days

Title

Relations plasma concentration-dose metoclopramide subcutaneously and intravenously

Description

Measured through their apparent clearances

Time Frame

13 days

Title

Cutaneous inflammatory signs and subcutaneous at the puncture site

Time Frame

During 13 days

Title

Numeric scale ranging from 0 to 10 for nausea

Time Frame

During 13 days

Title

Number of vomiting in the dose level;

Time Frame

During 13 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Matthieu FRASCA, MD

Organizational Affiliation

University Hospital, Bordeaux

Official's Role

Principal Investigator

Facility Information:

Facility Name

Centre Hospitalier Universitaire de Bordeaux - St André

City

Bordeaux

State/Province

Aquitaine

ZIP/Postal Code

33000

Country

France

12. IPD Sharing Statement

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Subcutaneous Route and Pharmacology of Metoclopramide

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