E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HIV plus bariatric surgery |
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E.1.1.1 | Medical condition in easily understood language |
HIV and weight loss surgery |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Surgical Procedures, Operative [E04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10068341 |
E.1.2 | Term | HIV-1 infection |
E.1.2 | System Organ Class | 100000004862 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10068900 |
E.1.2 | Term | Bariatric surgery |
E.1.2 | System Organ Class | 100000004865 |
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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 assess the pharmacokinetics of Doravirine in patients prior to and after undergoing bariatric surgery |
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E.2.2 | Secondary objectives of the trial |
1- To assess the safety of DOR in patients prior to and after undergoing BS
2- To assess the viral response to DOR in patients prior to and after undergoing BS
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria:
- HIV-infected
- VL suppressed <40c/ml for at least 6 months, blips are allowed
- planned to have BS (GBP or SG)
- Able to sign informed consent
- Age > or equal to 18 years
- Using DOR for at least 4 weeks prior to BS with VL < 40 copies/mL prior to the surgery
7. Using doravirine for at least 4 weeks prior to bariatric surgery with no detectable viral load
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E.4 | Principal exclusion criteria |
Exclusion criteria:
- History or current evidence of any condition, therapy, laboratory abnormality or other circumstance that might confound the results of the study or interfere with the subject’s participation
- Requires or is anticipated to require any of the prohibited medications known to contradict/interact with DOR
- Has significant hypersensitivity or other contraindication to DOR
- Creatinine clearance <40 ml/min
- Severe liver dysfunction (Diagnosed liver cirrhosis: Child-Pugh C)
- Pregnancy or planning to be pregnant during first 6 months post BS.
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E.5 End points |
E.5.1 | Primary end point(s) |
- Geometric Mean and the 95% classical confidence interval of AUC0-24h, Cmax, C24h and median (range) of tmax for doravirine in HIV patients after bariatric surgery (full pk analysis, pre surgery and week 12 post-surgery analysis)
- Geometric Mean and the 95% classical confidence interval of doravirine at Ctrough concentrations at 24+/-4 h from last dose doravirine in patients undergoing bariatric surgery (week 4 and week 24 post bariatric surgery)
- The percentage of patients showing a HIV VL >40 copy/ml post bariatric surgery
- safety and tolerance of DOR post bariatric surgery |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Pharmacokinetics (PK) analysis as follows:
1st PK day (-4-0 week pre-BS) and 2nd PK day (week 12 post-BS), a full pharmacokinetic assessment will take place.
Blood samples will be taken at the following time points: t=0 (pre-dose), 0.5, 1.0, 1.5, 2, 3, 6, 8, and 24h post ingestion (9 samples).
On week 4 and week 24 post-BS: One blood samples will be collected at 24h ± 4h after the last doravirine intake (the end of the dosing interval).
Safety, HIV viral load and CD4 count: pre-surgery, week 4, 12 and week 24 post bariatric surgery
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E.5.2 | Secondary end point(s) |
Total weight, body mass index (BMI) and waist circumference will be collected to assess reduction in weight and excess BMI.
Overall clinical and laboratory data will be collected and summarized before and after surgery. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
BMI and weight at pre-surgery, week 12 and 24 post bariatric surgery.
Clinial and laboratory data at pre-surgery, week 12 and 24 post bariatric surgery. |
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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 | No |
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 | Yes |
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 | No |
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 | Yes |
E.8.2.3.1 | Comparator description |
Comparison of PK parameters between before and after the surgery. the patient is his own control |
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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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
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 | |
E.8.9.1 | In the Member State concerned months | 18 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 18 |