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 | Body processes [G] - Metabolic Phenomena [G03] |
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 |
To study how PXR activation by rifampicin affects HDL cholesterol metabolism |
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E.2.2 | Secondary objectives of the trial |
To study how PXR activation by rifampicin affects glucose metabolism and blood pressure regulation. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
The sub-study is designed to collect duodenal samples via gastroscopy to analyse the expression of duodenal cholesterol transporters. The subjects of the main study may choose to participate in the sub-study after giving a separate informed consent. |
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E.3 | Principal inclusion criteria |
Healthy volunteers
18-40 years of age
Body mass index (BMI) 18.5-30 kg/m2 |
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E.4 | Principal exclusion criteria |
Systolic pressure more than 150 mmHg
Any continuous medication (including birth control pills; hormonal intrauterine device, inhaled asthma medications, and topical treatments for skin diseases are permitted)
Any significant medical condition including any liver disease
Insensitivity to rifampicin
Pregnancy and breast feeding
History of difficult venipuncture
Alcohol and medicine abuse and drug use
Participation in any other pharmaceutical trial within one month of screening |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percent change of HDL2 fraction between baseline and week 4 compared across placebo and rifampicin arms.
For the sub-study: difference between rifampicin and placebo arms in the duodenal expression of cholesterol transporters. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline, week 4.
For the sub-study: week 4. |
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E.5.2 | Secondary end point(s) |
a) Difference between rifampicin and placebo arms in glucose, insulin and glucagon AUCs of oral glucose tolerance test.
b) Sex difference between rifampicin and placebo arms in glucagon AUCs of oral glucose tolerance test.
c) Percent change of cholesterol fractions other than HDL2 between rifampicin and placebo arms.
d) Difference between rifampicin and placebo arms in fecal cholesterol fractions and bile acids.
e) Difference between rifampicin and placebo arms in office blood pressure, plasma renin activity, aldosterone and angiotensin II.
f) Percent change of flow-mediated dilatation and heart rate variability.
g) Difference between rifampicin and placebo arms in day-urine metanephrine, normetanephrine, and aldosterone excretion. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
a) Week 4.
b) Week 4.
c) Baseline, week 4, 6, and 8.
d) Week 4 and 6.
e) At various timepoints during study.
f) Baseline and week 4.5.
g) Week 2 and week 4.5. |
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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 | 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 | 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 | Yes |
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.8.2.4 | 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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |