E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
To evaluate pharmacodynamic, pharmacokinetic and nerve-related morphometric differences of biological gender (male versus female) on nerve block characteristics |
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E.1.1.1 | Medical condition in easily understood language |
To evaluate the effect of the local anesthetic Naropin in female and male volunteers and to evaluate the differences of nerve block characteristics and blood levels of the drug between the two genders |
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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: - Pharmacokinetic characteristics (Cmax, tmax, t1/2, AUC0-6, AUC0-∞) - Duration of motor blockade - Onset time of sensory nerve blockade - Onset time of motor blockade - Diameter of the ulnar nerve (absolute and relative to the BMI) - Visibility of the ulnar nerve in ultrasound (Grey-tone analysis ulnar nerve relative to the surrounding tissue)
and differences in these parameters between the two genders |
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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 - 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 - Pregnancy (female volunteers) - 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 - Any psychiatric illnesses - 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 (>2 drinks/day, defined according to USDA Dietary Guidelines 2015) - 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) |
Primary Objective: Evaluation of the duration of sensory nerve blockade following the administration of Naropin |
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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, 45, 60 min after the block, and then every 30 min until complete recovery of sensory blockade.
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. |
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E.5.2 | Secondary end point(s) |
Secondary Objective: - Pharmacokinetic characteristics (Cmax, tmax, t1/2, AUC0-6, AUC0-∞) - Duration of motor blockade - Onset time of sensory nerve blockade - Onset time of motor blockade - Diameter of the ulnar nerve (absolute and relative to the BMI) - Visibility of the ulnar nerve in ultrasound (Grey-tone analysis ulnar nerve relative to the surrounding tissue) And comparison of these parameters between the two genders |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
A sample of blood will be drawn from an antecubital vein for the determination of plasma ropivacaine concentrations at baseline and 20, 40, 60, 120, 240 and 360 min after performance of nerve blockade (7 blood samples).
Motor testing will be performed at the following time points(min): Baseline, 2, 4, 6, 8, 10, 15, 20, 30, 45, 60 min after the block, and then every 30 min until complete recovery of motor blockade.
Onset time of sensory nerve blockade: Time from performance of blockade (injection of LA) to Pinprick = 0 in 4 from 5 predefined sensory areas of the ulnar nerve.
Onset time of motor nerve blockade: Time from performance of blockade (injection of LA) to motor score = 0
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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 | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
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 | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
prospective, single center, interim analysis after 12 male and 12 female participants |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
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 | 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 | |