Dose-finding PKPD Trial for RE02 in Healthy Subjects

Study Overview
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Brief Summary
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The goal of this clinical trial is to compare corresponding inter- and intraindividual pharmacokinetic and pharmacodynamic profiles including assessments of safety & tolerability of three different doses against a placebo control.

Detailed Description
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Participants will undergo a series of four study days with varying doses of RE02 and a placebo. The intervention is embedded in controlled environment and continuous psychological support. Pharmacokinetic and pharmacodynamic assessments are obtained over the course of 6 hours on each study visit to estimate dose-exposure relationship and drug-drug-interaction. Additionally, the occurrence of adverse events will be closely monitored throughout the whole study.

Official Title
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Double-blind, Randomized, Dose-response Study of RE02 in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: RE02
* Drug: Manitol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and capable to give informed consent for the participation in the study after it has been thoroughly explained Willing to refrain from drinking alcohol one day before testing days and caffeinated drinks at the testing days and from consuming psychoactive substances or other medications for 2 weeks before testing days and for the duration of the study Already experienced with psychedelic substances (at least 5 prior experiences - microdoses do not count) Able and willing to comply with all study requirements Informed consent form was signed Good knowledge of the German language Participant informs study physicians / project scientists about simultaneous treatment or therapy with other physicians and about current intake of psychotropic substances or medication Women of childbearing potential are required to use effective, established contraception, such as oral, injected or implanted hormonal methods of contraception, placement of an intrauterine device (IUD) or intrauterine system (IUS), barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository Exclusion Criteria: Previous significant adverse response to a hallucinogenic drug Participation in another study where pharmaceutical compounds will be given Presence of Axis I affective, anxiety, or dissociative disorders Present or antecedent diagnosis of bipolar disorder (I, II, not otherwise specified), schizophrenia, schizoaffective disorder, psychosis, or other disorders from the psychotic spectrum First-degree relatives with present or antecedent schizophrenia, schizoaffective disorder, or bipolar disorder type I History of head trauma, seizures, cancer, or cerebrovascular accidents Recent cardiac or brain surgery Current abuse of medication or psychotropic substances (including nicotine addiction) according to SCID I criteria Presence of major internal or neurological disorders (including sepsis, pheochromocytoma, thyrotoxicosis, drug-induced fibrosis, familiar or basilar artery migraine) Cardiovascular disease (hypertonia, coronary artery disease, heart insufficiency, myocardical infarction, coronary spastic angina) Peripheral vascular disease (thromboangiitis obliterans, luetic arteritis, severe arteriosclerosis, thrombophlebitis, Raynaud's disease) Cerebrovascular disease (e.g., stroke, intracranial bleeding / hemorrhage, intracranial aneurysm) Serious abnormalities in ECG or blood count/chemistry Liver or renal or pulmonary disease Current use of medications with significant interaction potential with MAOI (e.g., antidepressants, antipsychotics, psychostimulants, dopaminergic/serotonergic agents, anticonvulsants) high risk of adverse emotional or behavioral reaction based on investigator's clinical evaluation (e.g., evidence of serious personality disorder, serious current stressors, lack of social support)

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Manitol<br>* Placebo Comparator<br>|
| Active Comparator: Low dose of RE02<br> | Drug: RE02<br>* Low, medium or high dose of RE02<br>|
| Active Comparator: Moderate dose of RE02<br> | Drug: RE02<br>* Low, medium or high dose of RE02<br>|
| Active Comparator: High dose of RE02<br> | Drug: RE02<br>* Low, medium or high dose of RE02<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameter Cmax | Dose-dependent changes in Cmax of several doses of RE02 | Changes from baseline to study days 1,2,3,4 | 
| Pharmacokinetic parameter Area under the curve (AUC) | Dose-dependent changes in AUC of several doses of RE02. | Changes from baseline to study days 1,2,3,4 | 
| Pharmacokinetic parameter T1/2 | Dose-dependent changes in T1/2 of several doses of RE02. | Changes from baseline to study days 1,2,3,4 | 
| Incidence of Treatment-Emergent Adverse Events | Dose-dependent changes in incidence of adverse drug reactions | On study days 1,2,3,4 | 
| Blood count (Lab biochemistry) | Changes from baseline in blood count | Changes from baseline to End of Study, an average of 4 weeks | 
| Clinical chemistry (Lab biochemistry) | Changes from baseline in any clinical chemistry parameter with potential clinical relevance. | Changes from baseline to End of Study, an average of 4 weeks | 
| Blood coagulation (Lab biochemistry) | Changes from baseline in blood coagulation | Changes from baseline to End of Study, an average of 4 weeks | 
| QT interval (12-lead Electrocardiogram [ECG]) | Dose-dependent changes of QT intervals assessed by clinical 12-lead ECG) | Changes from baseline to study days 1,2,3,4 | 
| Blood pressure | Dose-dependent changes in systolic and diastolic blood pressure | Changes from baseline to study days 1,2,3,4 | 
| Heart rate | Dose-dependent changes in heart rate | Changes from baseline to study days 1,2,3,4 | 
| Temperature | Dose-dependent changes in temperature | Changes from baseline to study days 1,2,3,4 | 
| Subjective effects | Dose-dependent changes in trajectories of subjective effects | Changes from baseline to study days 1,2,3,4 |