Evaluation of the Safety and Pharmacokinetics of Oleander 4X in Healthy Volunteers

Study Overview
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Brief Summary
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The homeopathic medicine, Oleander 4X HPUS is indicated for temporary relief of symptoms associated with flu, such as muscle or body aches, headaches, chills and fever, cough, and congestion. The primary purpose of this study is to assess the safety of Oleander 4X HPUS in health male and female subjects compared to a placebo. This is a randomized, double blind, placebo-controlled Phase I Proof of Concept clinical trial to evaluate the safety and efficacy of OLEANDER 4X HPUS in Healthy Volunteers. Briefly, 45 Healthy volunteers who meet the eligibility criteria and agree to participation in the study will be placed on 1.0 mL of OLEANDER 4X HPUS, four-to-twelve times per day for seven days. For the pharmacokinetics study (cohorts 4-6), participants will take OLEANDER 4X HPUS at a prescribed dose one time. The aim of the present study is to evaluate the safety of OLEANDER 4X HPUS. This real-world cohort provides a unique opportunity to study this medicine. This protocol outlines a study involving Healthy volunteers. Up to 45 volunteers will be recruited in specific health systems in the USA. Second ARM, sub-study: As a second arm of this study, a random double blind, placebo-controlled pharmacokinetics study in healthy volunteers. Briefly, 15 healthy volunteers who meet the same eligibility criteria and agree to participation in the study will be placed on one, two, or 4 doses (1 mL per dose) of OLEANDER 4X HPUS one time. This is effectively three ascending doses in 4 subjects on OLEANDER 4X HPUS, compared to the placebo (1 subject).

Detailed Description
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The aim of the present study is to evaluate the safety of OLEANDER 4X HPUS. This protocol outlines a study involving Healthy volunteers. Up to 45 volunteers will be recruited in the USA. Second ARM, sub-study: As a second arm of this study, a random double blind, placebo-controlled pharmacokinetics study in healthy volunteers. Briefly, 15 healthy volunteers who meet the same eligibility criteria and agree to participation in the study will be placed on one, two, or 4 doses (1 mL per dose) of OLEANDER 4X HPUS one time. This is effectively three ascending doses in 4 subjects on OLEANDER 4X HPUS, compared to the placebo (1 subject).

Official Title
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A Phase 1, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Pharmacokinetics of Oleander 4X in Healthy Volunteers

Conditions
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Flu-like Symptoms

Intervention / Treatment
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* Drug: Oleander 4X - single
* Drug: Oleander 4X - double
* Drug: Oleander 4X - quadruple
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Volunteers. Subjects with no symptoms of respiratory illness such as fever, rhinorrhea, mild cough, sore throat, headache, fatigue, muscle pain, and malaise but with no shortness of breath. Male or non-pregnant female adult > 18 to 65 years of age at time of enrollment to include all races and ethnic minorities. Agree to the collection of blood specimens (for the pharmacokinetics study). Willingness of study participant to provide informed consent and accept randomization to any assigned treatment arm. Must agree not to enroll in another study of an investigational agent prior to Day 28 of study, unless hospitalized. Exclusion Criteria: Signs of any respiratory distress or pulmonary infection defined as the need for non-invasive or invasive mechanical ventilator support, ECMO or shock requiring vasopressor support. Subjects with risk factors for severe disease (e.g. hypertension, diabetes, pulmonary, cardiovascular, renal, hepatic, neurologic disease or immune compromise, obesity, and pregnancy). Any previous history of clinically significant cardiovascular disease, including ventricular arrhythmias. Current use of cardiac glycosides or a known allergic reaction to cardiac glycosides or compounds of similar chemical or biologic composition. Any risk factors that can lead to severe COVID-19 including uncontrolled diabetes, hypertension, and systemic diseases including hepatic disease and renal insufficiency. Pregnancy or breastfeeding. Participation in any other clinical trial of an experimental treatment for COVID-19.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a randomized, double-blind, placebo-controlled Phase I study that will investigate the safety and efficacy of OLEANDER 4X HPUS in Healthy Volunteers.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Safety of Oleander 4X HPUS<br>: To evaluate the clinical safety of OLEANDER 4X HPUS in healthy volunteers relative to the control arm (placebo group). | Drug: Oleander 4X - single<br>* Cohort 1 receive 4 doses of Oleander 4X in a 24-hour period for a period of seven days.<br>Drug: Oleander 4X - double<br>* Cohort 2 receive 2 doses of either active drug or placebo 4 times per day in a 24-hour period for a period of seven days.<br>Drug: Oleander 4X - quadruple<br>* Cohort 3 receive 4 doses of either active drug four times per day in a 24-hour period for a period of seven days.<br>Drug: Placebo<br>* The placebo group receives 4 doses of placebo in a 24-hour period for a period of 7 days<br>|
| Experimental: Pharmacokinetics evaluation of Oleander 4X HPUS<br>To evaluate the pharmacokinetics of OLEANDER 4X HPUS versus placebo. | Drug: Oleander 4X - single<br>* Cohort 1 receive 4 doses of Oleander 4X in a 24-hour period for a period of seven days.<br>Drug: Oleander 4X - double<br>* Cohort 2 receive 2 doses of either active drug or placebo 4 times per day in a 24-hour period for a period of seven days.<br>Drug: Oleander 4X - quadruple<br>* Cohort 3 receive 4 doses of either active drug four times per day in a 24-hour period for a period of seven days.<br>Drug: Placebo<br>* The placebo group receives 4 doses of placebo in a 24-hour period for a period of 7 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events, serious event, and any related reactions as assessed by CTCAE v5.0. |  | 1-7 days | 
| proportion of subjects undergoing DLT events | Safety evaluation | 1-7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pharmacokinetic parameters - AreaUnderCUrve (AUCt) [Time Frame: 24 hours] | AUCt plasma concentration of oleander (using Oleandrin as the marker) during 24 hours after administration. | 0-24 hours | 
| half-life (t1/2) | half-life (t1/2) of oleander extract (using Oleandrin as the marker) during 24 hours after administration. | 0-24 hours | 
| maximum and minimum plasma concentration | maximum and minimum plasma concentration of oleander extract (using Oleandrin as the marker) during 24 hours after administration. | 0-24 hours | 
| total body clearance (Cltot) | total body clearance (Cltot) of oleander extract (using Oleandrin as the marker) during 24 hours after administration. | 0-24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Flu-like symptoms, Avila Herbals, Phoenix Biotechnology