E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
To evaluate the pharmacodynamic effects of perineural administered liposomal bupivacaine on nerve block characteristics |
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E.1.1.1 | Medical condition in easily understood language |
To evaluate the characteristics of a long-actin local anaesthetic, when administered around a nerve |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03] |
MedDRA Classification |
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 |
Primary Objective: Duration of sensory nerve blockade
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E.2.2 | Secondary objectives of the trial |
Secondary Objective: Duration of motor blockade Onset time of sensory nerve blockade Onset time of motor blockade |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Healthy males and females • Healthy, according to the medical history, ECG, vital signs, laboratory results and physical examination as determined by the Investigator/Sub-Investigator • Signed written informed consent prior to inclusion in the study • 18-55 years old inclusive • Clearly detectable ulnar nerve at the non-dominant arm in ultrasound evaluation, according to the main investigators’ opinion • BMI: 18 to 35 kg/m2 • Ability to understand the full nature and purpose of the study, including possible risks and side effects • Ability to co-operate with the investigator and to comply with the requirements of the entire study • Availability to volunteer for the entire study duration and willing to adhere to all protocol requirements |
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E.4 | Principal exclusion criteria |
• Any clinically relevant abnormalities at ECG (12 leads) • Any clinically relevant abnormal physical findings • Any clinically relevant abnormal laboratory values indicative of physical illness • Ascertained or presumptive hypersensitivity to the active principle and/or formulations ingredients of the study drug • History of anaphylaxis to drugs or allergic reactions in general, which the investigator considers may affect the outcome of the study • If one of the investigated nerves are not clearly visible in ultrasound • Relevant history of malignancy, of renal, hepatic, cardiovascular, respiratory, gastrointestinal, musculoskeletal, skin (particularly at the site of drug application), haematological, endocrine or neurological diseases that may interfere with the aim of the study • Pregnancy and breastfeeding • Any psychiatric illnesses • Any anticoagulatory or pain-therapy-related drugs (e.g. NSAIDs, opioids) from one week before until the end of the study • Using other medications during 1 week before the start of IMP application including OTC • Participation in another clinical study investigating another IMP within 1 month prior to screening • Blood donations during 4 weeks prior to this study • History of drug or alcohol abuse (more than 2 glasses of either a small beer, 1/8 L wine or 2 cL spirits per day) • Other objections to study participation in the opinion of the investigator
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E.5 End points |
E.5.1 | Primary end point(s) |
To assess the nerve block the following tests will be performed: Sensory blockade will be evaluated via Pinprick testing (0 = no sensory feeling, 100 = no difference in sensory feeling to the corresponding non-blocked side) at the hypothenar area compared with the corresponding non-blocked side. Motor blockade will be evaluated via adduction of the thumb: - 3 = no difference, adduction against contra-force possible - 2 = slight difference, adduction against slight contra-force hardly possible - 1 = significant difference, adduction without contra-force hardly possible - 0 = no active adduction possible, paralysis
Onset of sensory and motor block is defined as Pinprick = 0 in the hypothenar area (4 from 5 above-described areas to consider anatomical variations) and motor scale = 0. Duration of sensory and motor block is defined as Pinprick testing = back to 80 in the hypothenar area and motor scale = back to 1.
The primary endpoint is the duration of sensory block and it is defined as Pinprick testing = 80 in the hypothenar area.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Sensory testing will be performed at the following time points (min): Baseline, 2, 4, 6, 8, 10, 15, 20, 30, 60 min after the block, and then every 60 min until Pinprick testing = 80.
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E.5.2 | Secondary end point(s) |
Duration of motor block Onset time of sensory nerve blockade Onset time of motor blockade |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Sensory and motor testing will be performed at the following time points (min): Baseline, 2, 4, 6, 8, 10, 15, 20, 30, 60 min after the block, and then every 60 min until Pinprick testing = 80 and motor-scale = 1. Onset of sensory and motor block is defined as Pinprick = 0 in the hypothenar area (4 from 5 above-described areas to consider anatomical variations) and motor scale = 0. Duration of motor block is defined as motor scale = back to 1. |
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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 | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | No |
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 | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |