E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The study will be carried out in patients with primary open angle glaucoma and healthy subjects |
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E.1.1.1 | Medical condition in easily understood language |
The study will be carried out in patients with primary open angle glaucoma and healthy subjects |
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E.1.1.2 | Therapeutic area | Body processes [G] - Ocular Physiological Phenomena [G14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036719 |
E.1.2 | Term | Primary open angle glaucoma |
E.1.2 | System Organ Class | 100000004853 |
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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 investigate the effect of single administration of Tetrahydrocannabinol (THC) on ocular blood flow and its regulation in patients with primary open angle glaucoma and healthy subjects. |
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E.2.2 | Secondary objectives of the trial |
• Flicker induced increase in retinal blood flow • Retinal vessel diameters • Retinal blood velocities • Retinal oxygen saturation • Retinal vessel density • Dronabinol concentration in plasma, tear fluid and finger sweat • Normalized blur (LSFG) • Relative flow volume (LSFG) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria for patients with primary open angle glaucoma: • Diagnosis of manifest open angle glaucoma as defined as pathological optic disc appearance, glaucoma hemifield test outside normal limits and/or untreated IOP ≥ 21 mmHg on at least three measurements in the medical history. • Mean deviation in the visual field test < 10dB • Informed consent signed and dated • Patient aged ≥ 18 years old • Ametropia ≤ 6 diopters • Normal findings in the medical history and physical examination including ECG unless the investigator considers an abnormality to be clinically irrelevant • Normal findings in the laboratory testing unless the investigator considers an abnormality to be clinically irrelevant • Nonsmokers
Inclusion criteria for healthy subjects: • Men and women aged ≥ 18 years old • Ametropia ≤ 6 diopters • Informed consent signed and dated • Normal findings in the medical history and physical examination including ECG unless the investigator considers an abnormality to be clinically irrelevant • Normal findings in the laboratory testing unless the investigator considers an abnormality to be clinically irrelevant • Non-smokers
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E.4 | Principal exclusion criteria |
Exclusion criteria for patients with primary open angle glaucoma: • Exfoliation glaucoma • Pigmentary glaucoma • Secondary glaucoma • History of acute angle closure • Intraocular surgery within the last 6 months • Filtration surgery for glaucoma at any time • Laser procedure for glaucoma within the last 12 months • Visual field not performed or not available within 6 months • Ocular inflammation or infection within the last 3 months • Regular use of medication that potentially could interact with THC, abuse of alcoholic beverages or drugs • History of drug or alcohol abuse • Psychiatric disorders in the medical history • Risk for drug dependence as evaluated by a psychiatrist • Participation in a clinical trial in the 3 weeks preceding the study • Positive urine drug test at the screening examination or on the study days • Positive alcohol breath test at the screening examination or on the study days • Regular consumption of cannabis and inability to not consume cannabis during the study period • Symptoms of a clinically relevant illness in the 3 weeks before the first study day • History or presence of gastrointestinal, liver or kidney disease, or other conditions known to interfere with distribution, metabolism or excretion of study drugs • Blood donation during the previous 3 weeks • Known hypersensitivity to any of the components of the IMP under investigation or other study medication • History or family history of epilepsy • Pregnant or breast-feeding women • Women of childbearing potential (neither menopausal, nor hysterectomized, nor sterilized) not using effective contraception (oral contraceptives, intra-uterine device, contraceptive implant or condoms)
Exclusion criteria for healthy subjects: • Ocular inflammation or infection within the last 3 months • Regular use of medication that potentially could interact with THC • Abuse of alcoholic beverages or drugs • History of drug or alcohol abuse • Psychiatric disorders in the medical history • Risk for drug dependence as evaluated by a psychiatrist • Participation in a clinical trial in the 3 weeks preceding the study • Positive urine drug test at the screening examination or on the study days • Positive alcohol breath test at the screening examination or on the study days • Regular consumption of cannabis and inability to not consume cannabis during the study period • Symptoms of a clinically relevant illness in the 3 weeks before the first study day • History or presence of gastrointestinal, liver or kidney disease, or other conditions known to interfere with distribution, metabolism or excretion of study drugs • Blood donation during the previous 3 weeks • Known hypersensitivity to any of the components of the IMP under investigation or other study medication • History or family history of epilepsy • Pregnant or breast-feeding women • Women of childbearing potential (neither menopausal, nor hysterectomized, nor sterilized) not using effective contraception (oral contraceptives, intra-uterine device, contraceptive implant or condoms)
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E.5 End points |
E.5.1 | Primary end point(s) |
Optic nerve head blood flow |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Since this is a cross-over study, optic nerve head blood flow will be assessed on both study days before and after administration of dronabinol or placebo. |
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E.5.2 | Secondary end point(s) |
• Flicker induced increase in retinal blood flow • Retinal vessel diameters • Retinal blood velocities • Retinal oxygen saturation • Retinal vessel density • Dronabinol concentration in plasma, tear fluid and finger sweat • Normalized blur (LSFG) • Relative flow volume (LSFG) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Since this is a cross-over study, optic nerve head blood flow will be assessed on both study days before and after administration of dronabinol or placebo. |
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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 | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
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 | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |