Efficacy and Safety of Emodepside in Adults Infected With Trichuris Trichiura and Hookworm

Study Overview
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Brief Summary
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The rationale of the study is to provide evidence on the efficacy and safety of Emodepside in adults infected with Trichuris trichiura and hookworm.

Official Title
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Efficacy and Safety of Emodepside in Adults Infected With Trichuris Trichiura and Hookworm: Randomized Two Stages Phase II Seamless Adaptive Controlled Single-blind Trials

Conditions
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Trichuris Trichiura; Infection, Hookworm Infections

Intervention / Treatment
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* Drug: Emodepside


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female adults aged between 18 and 45 years Written and signed informed consent Examined by a study physician before treatment Provided two stool samples at baseline Trichuris trichiura and hookworm EPG ≥ 48 and at least two Kato-Katz thick smears slides with more than one Trichuris trichiura and hookworm eggs Exclusion Criteria: Pregnant or lactating and/or planning to become pregnant within three months after drug treatment Type 1 and/or 2 diabetes Psychiatric disorders History of ophthalmological conditions Presence or history of major systemic or chronic illnesses, as assessed by a medical doctor, during initial clinical assessment Suffers from severe anaemia (Hb < 80 g/l) Received anthelminthic treatment within past four weeks Attending other clinical trials during the study Received strong CYP3A4 inducers or inhibitors as well as concomitant treatments that are relevant substrate for CYP3A4 such as clarithromycin, erythromycin and rifampicin Received strong P-gp inhibitors as well as concomitant treatments that are relevant substrates for P-gp such as clotrimazole and ritonavir

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Emodepside 5 mg<br> | Drug: Emodepside<br>* Treatment with ascending doses of emodepside (from 5 mg to 30 mg) or albendazole (400 mg) or placebo.<br>|
| Experimental: Emodepside 10 mg<br> | Drug: Emodepside<br>* Treatment with ascending doses of emodepside (from 5 mg to 30 mg) or albendazole (400 mg) or placebo.<br>|
| Experimental: Emodepside 15 mg<br> | Drug: Emodepside<br>* Treatment with ascending doses of emodepside (from 5 mg to 30 mg) or albendazole (400 mg) or placebo.<br>|
| Experimental: Emodepside 20 mg<br> | Drug: Emodepside<br>* Treatment with ascending doses of emodepside (from 5 mg to 30 mg) or albendazole (400 mg) or placebo.<br>|
| Experimental: Emodepside 25 mg<br> | Drug: Emodepside<br>* Treatment with ascending doses of emodepside (from 5 mg to 30 mg) or albendazole (400 mg) or placebo.<br>|
| Experimental: Emodepside 30 mg<br> | Drug: Emodepside<br>* Treatment with ascending doses of emodepside (from 5 mg to 30 mg) or albendazole (400 mg) or placebo.<br>|
| Active Comparator: Albendazole<br> | Drug: Emodepside<br>* Treatment with ascending doses of emodepside (from 5 mg to 30 mg) or albendazole (400 mg) or placebo.<br>|
| Placebo Comparator: Placebo<br> | Drug: Emodepside<br>* Treatment with ascending doses of emodepside (from 5 mg to 30 mg) or albendazole (400 mg) or placebo.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cure rate (CR) of emodepside against Trichuris trichiura | CR will be calculated as the percentage of Trichuris trichiura egg-positive participants at baseline who become egg-negative after treatment. | In the week between 14 and 21 days post-treatment | 
| Cure rate (CR) of emodepside against hookworm | CR will be calculated as the percentage of hookworm egg-positive participants at baseline who become egg-negative after treatment. | In the week between 14 and 21 days post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Egg Reduction Rate (ERR) of the emodepside against Trichuris trichiura and hookworm. | Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. The egg reduction rate (ERR) is calculated as follows: ERR = (1-(geometric mean EPG at follow-up/geometric mean EPG at baseline))*100). Note: in contrast to the publication the outcome measure entry mask requires the complementary percentage: (geometric mean at follow-up/geometric mean at baseline)*100). | In the week between 14 and 21 days post-treatment | 
| CR against Ascaris lumbricoides | CR will be calculated as the percentage of Ascaris lumbricoides egg-positive participants at baseline who become egg-negative after treatment. | In the week between 14 and 21 days post-treatment | 
| ERR against Ascaris lumbricoides | Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. The egg reduction rate (ERR) is calculated as follows: ERR = (1-(geometric mean EPG at follow-up/geometric mean EPG at baseline))*100). Note: in contrast to the publication the outcome measure entry mask requires the complementary percentage: (geometric mean at follow-up/geometric mean at baseline)*100). | In the week between 14 and 21 days post-treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Emodepside, Trichuris trichiura, Hookworm, Soil-transmitted helminths, Efficacy, Safety, Dose selection