Pain therapeutics, neuropathic pain, nociceptive pain, synergism between opioids and TCA. MedDRA version: 14.1 Level: LLT Classification code 10054095 Term: Neuropathic pain System Organ Class: 10029205 - Nervous system disorders MedDRA version: 14.1 Level: LLT Classification code 10066714 Term: Acute pain System Organ Class: 10018065 - General disorders and administration site conditions
Conditions
Interventions
Trade Name: Temgesic
Product Name: Buprenorpine
Product Code: RVG 08725
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: BUPRENORPHINE
CAS Number: 52485-79-7
Current Sponsor code: Temge
Sponsors
Dr. Reddy's Laboratories Ltd.
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Caucasian (white) males aged between 18 and 45 years (inclusive) at screening with no clinically significant findings on the physical examination. 2. Signed informed consent prior to any study-mandated procedure. 3. Body mass index (BMI) between 18 and 30 kg/m2 (inclusive) at screening. 4. Systolic blood pressure (SBP) 100–140 mmHg, diastolic blood pressure (DBP) 60–90 mmHg, and heart rate (HR) 45–90 b.p.m. (all inclusive). 5. 12-lead electrocardiogram (ECG) without clinically relevant abnormalities at screening. 6. Haematology and clinical chemistry results within normal range to a clinically relevant extent at screening. 7. Negative results from urine drug screen at screening. 8. Ability to communicate well with the investigator and to understand and comply with the requirements of the study. All clinical judgments will be done by the study physician and he or she will decide eligibility of the subjects based on individual evaluation for each case. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 10 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Known hypersensitivity to any excipients of the drug formulations. 2. Previous treatment with any prescribed or OTC medications (including herbal medicines such as St John’s Wort), within 7 days prior to screening. 3. Treatment with another investigational drug within 3 months prior to screening. 4. History or clinical evidence of alcoholism or drug abuse. 5. Treatment with or consumption of inducers or inhibitors of CYP3A4 (e.g. grapefruit (juice), star fruit) or CYP2C8. 6. Excessive caffeine consumption, defined as = 800 mg per day at screening. 7. History or clinical evidence of any disease, and/or existence of any surgical or medical condition, which might interfere with the absorption, distribution, metabolism or excretion of the study drugs. 8. Smoking within 3 months prior to screening and inability to refrain from smoking during the course of study. 9. Loss of 250 mL or more of blood within 3 months prior to screening. 10. Positive results from the hepatitis serology (except in the case of VHB for vaccinated subjects) at screening. 11. Positive results from the HIV serology at screening. 12. Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol. 13. Legal incapacity or limited legal capacity at screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To determine if co-administration of acute milnacipran with acute buprenorphine potentiates or synergises with the analgesic effects of buprenorphine in healthy volunteers or vice versa. ;Timepoint(s) of evaluation of this end point: Baseline and around 15 minutes after the end of the medication infusion.;Secondary Objective: • To determine if co-administration of multiple-dose milnacipran with acute buprenorphine potentiates or synergises with the analgesic effects of buprenorphine in healthy volunteers. • To investigate the safety and tolerability of co-administration of iv buprenorphine and oral milnacipran in healthy subjects. • To examine the potential pharmacokinetic interactions between of i.v. buprenorphine and oral milnacipran in healthy subjects. ;Primary end point(s): Safety & Tolerability Change from baseline: • vital signs (supine blood pressure [BP] and HR, SpO2 (saturation)) and body weight; • ECG variables; • clinical laboratory tests including urinalysis. • simple breath count/flow spirometry Treatment-emergent • ECG abnormalities 24 hours after study drug administration in each treatment period. • AEs up to 96 hours after study drug administration in each treatment period. • SAEs from (first) study drug administration up to EOS. Pharmacodynamics • Cold pressor test o Tolerance time (s) o Intensity x time AUC (%?s) Pharmacokinetics • Buprenorphine and nor-buprenorphine PK (LLOQ 0.2 ng/mL) • Milnacipran PK (1-1000 ng/mL, no separation of enantiomers) | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Baseline and around 15 minutes after the end of the medication infusion.;Secondary end point(s): SECONDARY ENDPOINTS Pharmacodynamics • Pupil size (pupil:iris ratio) [opioid sensitive] (2 min) • Pain threshold and tolerance levels for each nociceptive test: o Thermal grill (VAS) [neuropathic pain model] (2 min) o Pressure pain (muscle) (kPa), [fibromyalgia model (?)] (4 min) o Electrical pain (skin) (mA) single stimulus [SNRI sensitive] (4 min) o Cold pressor pain (seconds) (6 min) o Diffuse Noxious Inhibitory Control (difference of electrical pain before and after cold pressor task) (4 min) • Other CNS effects o Saccadic eye movement [SNRI sensitive] (3 min) o Body sway (postural stability) [opioid, SNRI sensitive] (3 min) o Adaptive Tracking (Motor Co-ordination/Attention) [opioid, SNRI sensitive] (4 min) | — |
Countries
Netherlands
Contacts
Public ContactGeert Jan Groeneveld
Cente for Human Drug Research
Outcome results
None listed