E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cannabinor is as an analgesic and anti-inflammatory agent. By its nature, it has been designed to be more active at the CB2 peripheral receptors and have less activity at the central CB1 receptors. Thus, by design, cannabinor is expected to have less psychotropic effect than natural cannabinoids, such as those found in cannabis (including THC). |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033371 |
E.1.2 | Term | Pain |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The purpose of the present study is to evaluate the analgesic efficacy of three dosages of cannabinor compared to placebo over 8 hours using the dental impaction acute pain model. The objectives of the present study are to evaluate the efficacy and safety of three dosages of cannabinor compared to placebo in an 8-hour study of dental pain following extraction of one mandibular or two ipsilateral impacted or partly impacted third molars. Following the surgical procedure, the efficacy of a single administration of any one of three doses of cannabinor or that of placebo will be evaluated. In case Pharmos decides to conduct an interim analysis based on the blinded data from the first 40 subjects, evaluation of two different dosages (instead of three) of cannabinor compared to placebo will be performed. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
a. Males 18 to 55 years of age; b. Patients scheduled to undergo surgical extraction of one or two ipsilateral impacted third molars, at least one of which must be at least a partial bony mandibular extraction; c. Use of only the following pre-operative medication(s)/ anesthetic(s): short-acting local anesthetic (mepivacaine or lidocaine) without a vasoconstrictor; d. Able to read, comprehend, and sign the consent form; e. Examined by the attending dentist and physician and medically cleared to participate in the study; f. In good general health with no contraindications to any of the study or rescue medications. g. Normal ECG with baseline QTcF < 450 msec
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E.4 | Principal exclusion criteria |
a. Presence of a serious medical condition (e.g., hypertension, poorly controlled diabetes, impaired cardiac, hyper- or hypothyroidism); b. Baseline QTcF>450 msec as measured in the screening ECG or family history of Long QT syndrome; c. Impaired renal or hepatic function as measured in the clinical safety laboratory test results in the screening visit; d. Presence of orthostatic hypotension upon screening. e. Need for continuous medical treatment within two weeks prior to study entry with the exception of L-thyroxin for continuous treatment of a hypothyreosis; f. Acute local infection at the time of surgery that could confound the post-surgical evaluation; g. Known CNS disturbance or history of seizure disorder; h. History of alcoholism or substance abuse or daily consumption of 5 or more alcohol-containing beverages; i. Habituation to analgesic drugs (i.e., routine use of oral analgesics 5 or more times per week for other but impacted wisdom tooth pain); j. Prior use of any prescription or nonprescription drug including analgesics such as NSAID (including aspirin, sedative, or CNS/ psychotropic) within 5 days of the surgical procedure, except for paracetamol and ibuprofen which can be used up to 2 days prior to the surgical procedure and pre-anesthetic medication and anesthesia for the procedure; k. Has ingested any caffeine-containing beverages, chocolate, or alcohol 4 hours or less before taking study medication; l. Has been treated for depression within the past 6 months; m. Has a family history of any psychiatric disorder or current psychiatric disorder. n. Has taken an investigational drug within the past 30 days; o. Can not refrain from smoking 4 hours before and during the duration of the stay at the investigational site; p. History of allergy to any cannabinoid-like product; q. Has previously been entered into this study; r. Study site or Sponsor employee or relative of an employee who is directly involved in the study. s. Unable to return for follow-up or comply with other study requirements in the opinion of the investigator. t. Seropositive for HIV antibodies HIV1 and HIV2, hepatitis B surface antigen (HBs-Ag) and hepatitis C antibody (Hep C Ab).
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E.5 End points |
E.5.1 | Primary end point(s) |
• TOTPAR 8: time weighted sum of Pain Relief Rating (PRR) scores over 8 hours; and • Duration of relief as measured by the time to rescue medication
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |