A dose-ascending, parallel group, randomised, double-blind, placebo-controlled pilot phase followed by a parallel group, randomised, double-blind, placebo-controlled phase to compare the effect of intravenous MR30507/09, MR30365/07 and fentanyl on respiratory responses, and an assessment of naloxone reversal and naltrexone blockade on MR30507/09 and MR30365/07 in healthy subjects

Completed

Conditions: ademhaling
Respiration

Registration Number: NL-OMON39546

Lead Sponsor: Mundipharma Research Limited

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 78

Inclusion Criteria

1. Written informed consent obtained.
2. Healthy male subjects aged 18 to 45 years inclusive.
3. Body weight ranging from 60 to 100 kg and a BMI >= 18 and <= 30
4. Healthy and free of significant abnormal findings as determined by medical history, physical examination, vital signs, laboratory tests and ECG.
5. Male subjects must be willing to use contraception with their partners throughout the study and for 30 days after completion of the study and agree to inform the Investigator if their partner becomes pregnant during this time
6. Subject is deemed suitable by the Investigator for inclusion in the study.

Exclusion Criteria

1. Any history of drug or alcohol abuse, or recreational drug use within 30 days prior to study drug administration.
2. Any history of conditions that might interfere with drug absorption, distribution, metabolism or excretion.
3. Use of opioid or opioid antagonist-containing medication in the past 90 days.
4. Any history of frequent nausea or vomiting regardless of etiology.
5. Any history of seizures or symptomatic head trauma.
6. Participation in a clinical drug study during the 90 days preceding the initial dose in this study.
7. In the Investigator*s opinion a clinically significant upper or lower respiratory infection within 4 weeks prior to the screening visit.
8. History of asthma, COPD, or other bronchial or lung diseases.
9. History of regurgitation or difficulty of intubation.
10. A history of additional risk factors for Torsades de Pointes (e.g. heart failure, hypokalaemia, personal or family history of long QT syndrome, syncope, or family history of sudden death).
11. Abnormal cardiac conditions including QTc interval greater than 450 msec at screening or pre-dose.
12. Use of medication within five times the half-life or minimum 14 days for prescription medication or 7 days for over-the-counter preparations (including vitamins, herbal and/or mineral supplements), whichever is longer, before the first dose of study treatment and during the study.
13. Refusal to abstain from food 6 hours preceding and 8 hours following study drug administration and to abstain from caffeine or xanthine containing beverages entirely during each confinement.
14. Weekly alcohol intake exceeding the equivalent of 21 units/week.
15. Consumption of alcoholic beverages within 24 hours before study drug administration, and refusal to abstain from alcohol for at least 48 hours after study drug administration.
16. History of heavy smoking (more than 20 cigarettes a day) within 45 days of study drug administration and refusal to abstain from smoking while in the study unit.
17. Blood or blood products donated within 90 days prior to study drug administration or any time during the study, except as required by this protocol.
18. Abnormal result obtained from Allen*s circulation test.
19. Positive results of urine drug screen, alcohol test, HBsAg, Hepatitis C antibody, or HIV tests.
20. Known sensitivity to fentanyl, opioids, naloxone, natrexone, or related compounds.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>• To determine the effect of MR30507/09 on ventilation in healthy subjects<br /><br>using the dynamic end-tidal forcing technique. • To obtain a dose-response<br /><br>relationship for the respiratory response effects of MR30507/09 and to compare<br /><br>this relationship with that of MR30365/07. • To assess MR30507/09 and<br /><br>MR30365/07 induced respiratory depression reversibility using naloxone IV<br /><br>injection. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>• To assess the safety and tolerability of MR30507/09 and MR30365/07. • To<br /><br>assess the PK of MR30507/09 and MR30365/07. • To assess arterial vs venous<br /><br>blood sampling in the concentration effect model.</p><br>