Generation of Biological Samples Positive to Hydromorphone for Anti-doping Control (HM)

Background:

Hydromorphone (HM) is a semi-synthetic derivative of morphine used for pain control. Like other opiates, due to its high potential of abuse HM is included on the World Anti-Doping Agency (WADA) list of prohibited substances.

Hypothesis:

The oral administration of hydromorphone hydrochloride in healthy subjects allows generating detectable concentrations of the drug in urine. Positive urine samples will enable to identify analytical strategies for doping control.

Objectives:

Primary objective: To measure the concentrations of hydromorphone in urine for anti-doping control samples.

Secondary objective: To identify metabolites and precursors of hydromorphone in urine. To assess safety and tolerability of the drug used.

Methods:

Phase I, open, non-randomized clinical trial, with a treatment condition (hydromorphone) administered orally to 2 subjects.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Hydromorphone Hydrochloride

Detailed Description

This study aims to characterize the patterns of urinary excretion of HM following the oral administration of 4 mg of hydromorphone hydrochloride (equivalent to 3.56 mg of hydromorphone). The detection of HM consumption can be done by urine immunoassay but several immunoassay tests are required to thoroughly detect synthetic, semi-synthetic and natural opioids due to the limited cross-reactivity of each assay. Therefore, superior test strategies are required to specifically identify low concentrations of opioids.

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

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08003
    • IMIM (Hospital del Mar Medical Research Institute)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Male volunteers aged between 18 and 45 years.
• Able to understand and accept the trial procedures and able to sign an informed consent.
• History and physical examination that demonstrate not presenting organic or psychiatric disorders.
• ECG, blood and urine tests performed before the test within normal limits. Minor or occasional variations of these limits will be allowed if, in the opinion of the Principal Investigator and taking into account the state of science, they have no clinical significance, do not pose a risk to the subject and do not interfere in the product evaluation. These variations and their non-relevance will be specifically justified sin writing.
• Body mass index (weight/height^2) between 19 and 25 kg/m2. BMI between 25 and 27 kg/m2 may be included according to Principal Investigator's criteria.

Exclusion Criteria:

• History of allergy, idiosyncrasy, hypersensitivity or adverse reactions to the active substance or similar nonapeptides, or to any of the excipients.
• Patients who have undergone surgical interventions and/or have had underlying diseases that could lead to a stricture of the gastrointestinal tract, that have "blind handles" of the gastrointestinal tract or gastrointestinal obstruction.
• Patients with severe decrease in liver function.
• Patients with respiratory failure or history of asthma crisis.
• Patients with acute abdominal pain of unknown origin.
• Background or clinical evidence of gastrointestinal, hepatic, renal disorder or others that may involve an alteration of the absorption, distribution, metabolism or excretion of the drug, or that are suggestive of gastrointestinal irritation by drugs.
• Background or clinical evidence of psychiatric disorders, alcoholism, drug abuse or habitual consumption of psychoactive drugs.
• Having participated in another clinical trial with medication in the three months prior to the start of the study.
• Having suffered some organic disease or major surgery in the six months prior to the start of the study.
• Antecedents or clinical evidence of cardiovascular, respiratory, renal, hepatic, endocrine, gastrointestinal, hematological, neurological or other acute or chronic diseases that, in the opinion of the Principal Investigator or the collaborators designated by him/her, may pose a risk to the subjects or may interfere with the objectives of the study. Especially epileptic seizures or a history of epilepsy.
• Having taken medication regularly in the month prior to the study sessions. Treatment with monoamine oxidase inhibitors (MAOIs), buprenorphine, nalbuphine or pentazocine during the two months prior to the study. Treatment with single doses of another type of symptomatic medication in the week prior to the study sessions will not be a reason for exclusion if it is assumed that the drug has been completely eliminated on the day of the experimental session.
• Smokers of more than 20 cigarettes a day in the 3 months before the study.
• Consumption of more than 20 g of alcohol daily in women and more than 40 g in men.
• Consumers of more than 5 coffees, teas, cola drinks, or other stimulant drinks or with xanthines daily in the 3 months prior to the study start.
• Being unable to understand the nature, consequences of the trial and the procedures that are asked to follow.
• Positive serology for hepatitis B, C or HIV.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment group; Subjects receive a single-dose treatment.Urine samples will be collected after administration (8 fractions: 0-4h, 4-8h, 8-12h, 12-24h, 24-36h, 36-48h, 48-60h, 60-72h post-administration).	Drug: Hydromorphone Hydrochloride; 4 mg of hydromorphone hydrochloride (equivalent to 3.56 mg of hydromorphone) administered orally in a single dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urine concentration of hydromorphone	Concentration of hydromorphone in fraction-1 urine samples	0-4 hours post-administration
Urine concentration of hydromorphone	Concentration of hydromorphone in fraction-2 urine samples	4-8 hours post-administration
Urine concentration of hydromorphone	Concentration of hydromorphone in fraction-3 urine samples	8-12 hours post-administration
Urine concentration of hydromorphone	Concentration of hydromorphone in fraction-4 urine samples	12-24 hours post-administration
Urine concentration of hydromorphone	Concentration of hydromorphone in fraction-5 urine samples	24-36 hours post-administration
Urine concentration of hydromorphone	Concentration of hydromorphone in fraction-6 urine samples	36-48 hours post-administration
Urine concentration of hydromorphone	Concentration of hydromorphone in fraction-7 urine samples	48-60 hours post-administration
Urine concentration of hydromorphone	Concentration of hydromorphone in fraction-8 urine samples	60-72 hours post-administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urine concentration of hydromorphone metabolites	Concentration of different hydromorphone metabolites in fraction-1 urine samples	0-4 hours post-administration
Urine concentration of hydromorphone metabolites	Concentration of different hydromorphone metabolites in fraction-2 urine samples	4-8 hours post-administration
Urine concentration of hydromorphone metabolites	Concentration of different hydromorphone metabolites in fraction-3 urine samples	8-12 hours post-administration
Urine concentration of hydromorphone metabolites	Concentration of different hydromorphone metabolites in fraction-4 urine samples	12-24 hours post-administration
Urine concentration of hydromorphone metabolites	Concentration of different hydromorphone metabolites in fraction-5 urine samples	24-36 hours post-administration
Urine concentration of hydromorphone metabolites	Concentration of different hydromorphone metabolites in fraction-6 urine samples	36-48 hours post-administration
Urine concentration of hydromorphone metabolites	Concentration of different hydromorphone metabolites in fraction-7 urine samples	48-60 hours post-administration
Urine concentration of hydromorphone metabolites	Concentration of different hydromorphone metabolites in fraction-8 urine samples	60-72 hours post-administration

Collaborators and Investigators

• Sponsor: Parc de Salut Mar
• Investigators: Principal Investigator: Ana M Aldea Perona, Dr, IMIM (Hospital del Mar Medical Research Institute)

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2019
• Primary Completion (Actual): December 18, 2019
• Study Completion (Actual): December 18, 2019

Study Registration Dates

• First Submitted: September 5, 2019
• First Submitted That Met QC Criteria: September 5, 2019
• First Posted (Actual): September 9, 2019

Study Record Updates

• Last Update Posted (Actual): December 23, 2019
• Last Update Submitted That Met QC Criteria: December 19, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Opiates; Hydromorphone; Anti-doping control
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Hydromorphone
• Other Study ID Numbers: IMIMFTCL/HM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No