E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10042609 |
E.1.2 | Term | Surgery |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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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 |
To evaluate the therapeutic equivalence, based on pharmacodynamic parameters, of Propofol 2% (20 mg/mL) MCT Fresenius and Diprivan® 20 mg/mL (AstraZeneca) administered by target-controlled infusion (TCI) |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety, tolerability, and pharmacokinetics (PK) of Propofol 2% (20 mg/mL) MCT Fresenius compared to Diprivan® 20 mg/mL (AstraZeneca) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female subjects ≥18 years and <65 years old
2. Able to understand and give signed and dated written informed consent
3. Body mass index (BMI) ≥20 and ≤30 kg/m2 at screening
4. ASA physical status 1 or 2
5. Undergoing elective, minor orthopaedic, vascular, urological, or gynaecological surgery |
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E.4 | Principal exclusion criteria |
1. The following planned procedures are to be excluded:
- Day surgery
- Emergency surgery
- Total hip or total knee replacement
- Requiring opening of the great cavities of the body (cranium, thorax, peritoneum, or pelvis)
- With routine risk, even if low, of haemorrhage severe enough to require administration or colloid or blood products
- With routine risk, even if low, of death during or soon after the procedure
- Vascular surgery involving the aorta, venae cavae, iliac arteries, or femoral arteries
2. Intended administration of IV medications through a central venous catheter
3. Administration of general anaesthesia or propofol within the 7 days prior to randomisation
4. History of hypersensitivity to propofol, eggs, Soya, peanuts, or any other constituent of the study drugs
5. ASA physical status ≥3
6. History of major anaesthesia complications
7. History of difficult airway management
8. History of difficult venous access
9. Myocardial infarction within 6 months of randomisation or a cardiac reperfusion procedure within 6 weeks of randomisation
10. Significant respiratory, cardiovascular, liver or renal disease as assessed by Investigator
11. Active systemic infection (localised infection related to surgical procedure is allowable as long as there is no indication of systemic involvement)
12. History of psychiatric disorder, including use of sedatives or antidepressants for any reason, within 6 months prior to randomisation
13. Alcohol or other substance abuse within 2 years prior to randomisation, as well as for the duration of the study
14. Use of medication that could reduce the subject’s respiratory and cardiac output |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Pharmacodynamic (PD) outcomes
- Predicted effect site propofol concentrations at time of LOER
- Time to BIS 50
- Predicted effect site propofol concentrations at time of BIS 50
Pharmacokinetic (PK) outcomes
- Plasma propofol concentration: pre-infusion, during infusion, and after infusion
- Mean estimated plasma propofol concentration at time of LOER
- Mean estimated plasma propofol concentration at time of BIS 50
- Mean estimated plasma propofol concentration at time of eye opening
Tolerability
- Pain at infusion site for anaesthesia induction
Safety outcomes
-Maximum percent change in mean arterial pressure (MAP) from baseline at time to LOER
- Maximum percent change in heart rate from baseline at time to LOER
- Mean intra-operative blood pressure
- Mean intra-operative heart rate
- 12-Lead ECG
- Time to eye opening
- Total propofol dose
- Total remifentanil dose
- Total ephedrine dose
- Total phenylephrine dose
- Post-operative nausea and vomiting
- Plasma lactate level at stop of the study drug infusion
- Day 1 adverse events (AEs)
- Days 7 to 14 AEs |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.6 | Pharmacokinetic | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Theurapeutic equivalence, tolerability |
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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) | Yes |
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 | No |
E.8.1.6 | Cross over | No |
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 | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
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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last visit of the last patient undergoing the study to be conducted in October 2013 |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |