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| Name | Class |
|---|---|
| Institute of Tropical Medicine, University of Tuebingen | OTHER |
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Study to evaluate the efficacy of DSM265 as a causal prophylactic in a standardized and validated Human Challenge model using direct venous inoculation of aseptic, purified, cryopreserved, vialed Plasmodium falciparum sporozoites.
This study follows the First In Human dose-escalation study of DSM265 (25 - 800 mg of DSM265) and an Induced-Blood Stage Malaria Challenge study (150 mg of DSM265) conducted in healthy adult volunteers in Australia. After identification of efficacious DSM265 plasma concentrations in the Induced-Blood Stage Malaria model, the current study will evaluate the efficacy of DSM265 as a causal prophylactic in a standardized and validated Human Challenge model using direct venous inoculation of aseptic, purified, cryopreserved, vialed Plasmodium falciparum sporozoites (Challenge).
Three sequential cohorts of healthy male and women volunteers, of non-childbearing potential or of childbearing potential with predefined accepted methods of contraception, are planned in order to investigate three preventive conditions with regard to administration of DSM265. Preventive administration of the study drug will occur 1 and 7 days before inoculum of Plasmodium falciparum sporozoite Challenge, with a last cohort administered at a time point to be determined from the 2 previous cohorts but which will not exceed 28 days before the challenge. The study will also include a cohort where subjects will be treated with atovaquone-proguanil (Malarone®) using the approved regimen for chemoprophylaxis.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1a: DSM265/placebo, sporozoite inoculum | Experimental | DSM265 400mg / placebo Day -1, sporozoite inoculum Day 0 |
|
| Cohort 1b: Malarone, sporozoite inoculum | Active Comparator | Malarone daily for 9 days from Day -1 to Day 7, sporozoite inoculum Day 0 |
|
| Cohort 2: DSM265/placebo, sporozoite inoculum | Experimental | DSM265 400mg / placebo Day -7, sporozoite inoculum Day 0 |
|
| Cohort 3: DSM265 / placebo, sporozoite inoculum (Optional) | Experimental | DSM265 400mg / placebo Day -X, sporozoite inoculum Day 0 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| DSM265 400mg | Drug | DSM265 400mg, single oral administration in a fed state |
|
| Measure | Description | Time Frame |
|---|---|---|
| Infection Rate | The infection rate is the number (percentage) of subjects in a cohort who became positive for parasitemia. Complete protection = Subjects with pre-patent period equal to 28 days. | Day 0 to Day 28 post-inoculum (daily) |
| Pre-patent Period | The pre-patent period is defined as the time (days) from inoculation with PfSPZ to first occurrence of a positive TBS. If no positive TBS is seen by Day 28, this variable is set to 28 days. Complete protection = Subjects showing with pre-patent period equal to 28 days. | Day 0 to Day 28 post-inoculum (daily) |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events as a Measure of Safety & Tolerability of DSM265 | Safety & tolerability of DSM265 for causal and suppressive chemoprophylaxis in non-immune healthy volunteers in a non-immune healthy volunteers in CHMI with PfSPZ challenge. | From first dose (Day -1 in Cohort 1A and Day -7 in Cohort 2) to Day 60 post-inoculum |
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Inclusion Criteria:
Good health based on medical history and physical examination- Body mass index >18 and <30 kg/m2
Lab results without clinically significant findings in 28 days prior to enrolment
Negative drug screening test
Females: negative pregnancy test at screening and on the day before first dose of DSM265 and sporozoite challenge injection
Sexually active males must agree to use a medically acceptable form of contraception from enrolment and continue for 12 weeks after the dose of DSM265
Women may only be included if they are either Identified as not of child bearing potential, or if of child bearing potential and willing and able to practice one of the continuous acceptable methods of contraception (must be one with failure rate less than 1% per year) with double barrier protection:
Agree to allow the investigators to discuss the medical history with General Practitioner and to sign a request to release medical information concerning contra-indications for participation in the study
Able and willing to comply with all study requirements for the duration of the study
Agree to undergo all study procedures, to attend all study visits and stay overnight for observation if required, up to last follow up visit
Willing to undergo a sporozoite challenge
Able and willing to answer all questions on the informed consent quiz correctly demonstrating an understanding of the meaning and of the study procedures
Able and willing to sign the informed consent form
Reachable (24/7) by mobile phone or email during the whole study period
Agree to refrain from blood donation during the course of the study and after the end of involvement in the study according to the local and national blood banking eligibility criteria (currently 4 years in Germany)
Willing to take a curative regimen of Riamet or another registered antimalarial if necessary
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Benjamin Mordmüller, Dr. med | Institut für Tropenmedizin, Uni. of Tübingen | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Universitätsklinikum Tübingen, Institut für Tropenmedizin | Tübingen | 72074 | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28363637 | Result | Sulyok M, Ruckle T, Roth A, Murbeth RE, Chalon S, Kerr N, Samec SS, Gobeau N, Calle CL, Ibanez J, Sulyok Z, Held J, Gebru T, Granados P, Bruckner S, Nguetse C, Mengue J, Lalremruata A, Sim BKL, Hoffman SL, Mohrle JJ, Kremsner PG, Mordmuller B. DSM265 for Plasmodium falciparum chemoprophylaxis: a randomised, double blinded, phase 1 trial with controlled human malaria infection. Lancet Infect Dis. 2017 Jun;17(6):636-644. doi: 10.1016/S1473-3099(17)30139-1. Epub 2017 Mar 28. |
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One subject was allocated to treatment but did not receive any study medication due to an ECG abnormality discovered after randomization and, therefore, 21 out of 22 subjects received at least one dose of the study medications.
In agreement with the Safety Review Team, the Sponsor decided to close the study without progressing to conduct Cohort 3.
A total of 40 subjects were screened. Of these 22 (55.0%) were enrolled to participate in the study
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1A: 400 mg DSM265, Sporozoite Challenge | DSM265 400mg on Day -1, sporozoite challenge on Day 0 DSM265 400mg: single oral administration in a fed state Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation |
| FG001 | Cohort 1B: Malarone, Sporozoite Challenge | Malarone daily for 9 days from Day -1 to Day 7, sporozoite challenge Day 0 Malarone: 250 mg atovaquone, 100 mg proguanil hydrochloride Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation |
| FG002 | Cohort 2: 400 mg DSM265, Sporozoite Challenge | DSM265 400mg on Day -7, sporozoite challenge on Day 0 DSM265 400mg: single oral administration in a fed state Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation |
| FG003 | Placebo Cohorts 1A and 2, Sporozoite Challenge | Placebo to DSM265 400 mg on Day -1, sporozoite challenge on Day 0 Placebo: Single oral administration in a fed state Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
one subject in cohort 1A was excluded prior to dosing
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1A: 400 mg DSM265, Sporozoite Challenge | DSM265 400 mg on Day -1, sporozoite challenge on Day 0 DSM265 400 mg: single oral administration in a fed state Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation |
| BG001 | Cohort 1B: Malarone, Sporozoite Challenge |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Infection Rate | The infection rate is the number (percentage) of subjects in a cohort who became positive for parasitemia. Complete protection = Subjects with pre-patent period equal to 28 days. | All subjects who received both at least one dose of study medication and the PfSPZ challenge | Posted | Count of Participants | Participants | Day 0 to Day 28 post-inoculum (daily) |
|
Adverse event data were collected from the day of dosing until Day 60 following PfSPZ challenge: Cohort 1A: 61 days Cohort 1B (Malarone): 61 days Cohort 2: 68 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort 1A: 400 mg DSM265 (Day-1), Sporozoite Challenge (Day0) | DSM265 400 mg on Day -1, sporozoite challenge on Day 0 DSM265 400 mg: single oral administration in a fed state Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pulmonary embolism | Vascular disorders | Systematic Assessment | One SAE was reported (pulmonary embolism) which was considered to be unrelated to the study drug due to identified risk factors (oral contraception, transatlantic flight) and timing of event (34 days after treatment intake). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Haemolysis | Blood and lymphatic system disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jörg Möhrle | Medicines for Malaria Venture | +41 22 555 0330 | moehrlej@mmv.org |
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| ID | Term |
|---|---|
| D016778 | Malaria, Falciparum |
| D008288 | Malaria |
| ID | Term |
|---|---|
| D011528 | Protozoan Infections |
| D010272 | Parasitic Diseases |
| D007239 | Infections |
| D000096724 | Mosquito-Borne Diseases |
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| ID | Term |
|---|---|
| C000606979 | DSM265 |
| C109496 | atovaquone, proguanil drug combination |
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| Placebo to DSM265 400 mg | Drug | Placebo to DSM265 400mg, single oral administration in a fed state |
|
| Plasmodium falciparum sporozoite challenge | Biological | IV Plasmodium falciparum sporozoites (3200) by direct venous inoculation |
|
|
| Malarone | Drug | 250 mg atovaquone, 100 mg proguanil hydrochloride |
|
|
| Number of Participants With Treatment Emergent Adverse Events (TEAE) as a Measure of Safety & Tolerability of Malarone | Safety & tolerability of Malarone for causal and suppressive chemoprophylaxis in non-immune healthy volunteers in a Plasmodium falciparum sporozoite challenge. Measured by adverse events, laboratory data. Malarone® was administered as a single daily dose over a period of 9 days from Day -1 to Day 7. | From first dose (Day -1, Cohort 1b) to Day 60 post-inoculum |
| Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Plasmodium Falciparum Sporozoite Challenge Inoculum | Safety & tolerability of Plasmodium falciparum sporozoite challenge inoculum during DSM265 administration, and Malarone administration. Measured by adverse events, laboratory data | Day 0 to Day 60 post-inoculum |
| DSM265 Pharmacokinetics Profile - T Max | Pre-dose and post-dose during the period including Day 28 | From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculum |
| DSM265 Pharmacokinetics Profile - T 1/2 | Pre-dose and post-dose during the period including Day 28 | From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculum |
| DSM265 Pharmacokinetics Profile - C Max | Pre-dose and post-dose during the period including Day 28 | From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculum |
| DSM265 Pharmacokinetics Profile - AUC 0-∞, AUC 0-168h, and AUC 0-480h | Pre-dose and post-dose during the period including Day 28 for AUC 0-∞, AUC 0-168h, and AUC 0-480h | From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculum |
| DSM265 Pharmacokinetics Profile - CL/F | Pre-dose and post-dose during the period including Day 28 | From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculum |
| DSM265 Pharmacokinetics Profile - Vz/F | Pre-dose and post-dose during the period including Day 28 | From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculum |
| DSM450 Pharmacokinetics Profile - T Max | Pre-dose and post-dose during the period including Day 28 | From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculum |
| DSM450 Pharmacokinetics Profile - Cmax | Pre-dose and post-dose during the period including Day 28 | From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculum |
| DSM450 Pharmacokinetics Profile - AUC 0-t, AUC 0-168h, and AUC 0-480h | Pre-dose and post-dose during the period including Day 28 for AUC 0-t, AUC 0-168h, and AUC 0-480h | From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculum |
| The Pharmacokinetic-pharmacodynamic Profile of Pre-administration of DSM265 on Clearance of Plasmodium Falciparum Parasites After Administration of the Sporozoite Challenge | The profile of plasma concentrations and pharmacokinetic parameters (AUC, Cmax, Tmax, T0-inf, AUC0-t, t1/2) will be reviewed on a background of the safety profile (adverse events, laboratory and ECG data) and the clearance of Plasmodium falciparum parasites (efficacy) after administration of the sporozoite challenge | From first dose of DSM265 (Day -1 in Cohort 1a, Day -7 in Cohort 2 and Day -X in Cohort 3) to 480 hours post-dose |
| Recrudescence of Parasite Kinetics Following DSM265 Administration. | On any re-appearance of parasites, thick smears and PCR samples will be examined to determine whether the parasite is a different variant(recrudescence) or has the same genetic profile as the original infection (re-infection) post-dose | Day 6 post-inoculum to Day 60 |
Malarone daily for 9 days from Day -1 to Day 7, sporozoite challenge Day 0 Malarone: 250 mg atovaquone, 100 mg proguanil hydrochloride Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation |
| BG002 | Cohort 2: 400 mg DSM265, Sporozoite Challenge | DSM265 400 mg on Day -7, sporozoite challenge on Day 0 DSM265 400 mg: single oral administration in a fed state Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation |
| BG003 | Placebo Cohorts 1A and 2 | Placebo to DSM265 400 mg on Day -7, sporozoite challenge on Day 0 Placebo to DSM265 400 mg: single oral administration in a fed state Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
Malarone daily for 9 days from Day -1 to Day 7, sporozoite challenge Day 0 Malarone: 250 mg atovaquone, 100 mg proguanil hydrochloride Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation |
| OG002 | Cohort 2: 400 mg DSM265 (Day-7), Sporozoite Challenge (Day0) | DSM265 400 mg on Day -7, sporozoite challenge on Day 0 DSM265 400 mg: single oral administration in a fed state Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation |
| OG003 | Placebo Cohorts 1A and 2 | Placebo to DSM265 400 mg on Day -7 or Day -1, sporozoite challenge on Day 0 Placebo to DSM265 400 mg: single oral administration in a fed state Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation |
|
|
| Primary | Pre-patent Period | The pre-patent period is defined as the time (days) from inoculation with PfSPZ to first occurrence of a positive TBS. If no positive TBS is seen by Day 28, this variable is set to 28 days. Complete protection = Subjects showing with pre-patent period equal to 28 days. | All subjects who received both at least one dose of study medication and the PfSPZ challenge | Posted | Geometric Mean | Geometric Coefficient of Variation | Days | Day 0 to Day 28 post-inoculum (daily) |
|
|
|
| Secondary | Number of Participants With Adverse Events as a Measure of Safety & Tolerability of DSM265 | Safety & tolerability of DSM265 for causal and suppressive chemoprophylaxis in non-immune healthy volunteers in a non-immune healthy volunteers in CHMI with PfSPZ challenge. | All the subjects included in the safety population were administered the study medication. | Posted | Count of Participants | Participants | From first dose (Day -1 in Cohort 1A and Day -7 in Cohort 2) to Day 60 post-inoculum |
|
|
|
| Secondary | Number of Participants With Treatment Emergent Adverse Events (TEAE) as a Measure of Safety & Tolerability of Malarone | Safety & tolerability of Malarone for causal and suppressive chemoprophylaxis in non-immune healthy volunteers in a Plasmodium falciparum sporozoite challenge. Measured by adverse events, laboratory data. Malarone® was administered as a single daily dose over a period of 9 days from Day -1 to Day 7. | All the subjects included in the safety population were administered the study medication. | Posted | Count of Participants | Participants | From first dose (Day -1, Cohort 1b) to Day 60 post-inoculum |
|
|
|
| Secondary | Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Plasmodium Falciparum Sporozoite Challenge Inoculum | Safety & tolerability of Plasmodium falciparum sporozoite challenge inoculum during DSM265 administration, and Malarone administration. Measured by adverse events, laboratory data | All the subjects included in the safety population were administered the study medication. | Posted | Count of Participants | Participants | Day 0 to Day 60 post-inoculum |
|
|
|
| Secondary | DSM265 Pharmacokinetics Profile - T Max | Pre-dose and post-dose during the period including Day 28 | All subjects who received study drug and provided they had sufficient DSM265 and/or DSM450 concentration data for the non-compartmental analysis were included in the pharmacokinetic analysis (all-treated set). | Posted | Median | Full Range | hours | From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculum |
|
|
|
| Secondary | DSM265 Pharmacokinetics Profile - T 1/2 | Pre-dose and post-dose during the period including Day 28 | All subjects who received study drug and provided they had sufficient DSM265 and/or DSM450 concentration data for the non-compartmental analysis were included in the pharmacokinetic analysis (all-treated set). | Posted | Geometric Mean | Geometric Coefficient of Variation | hours | From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculum |
|
|
|
| Secondary | DSM265 Pharmacokinetics Profile - C Max | Pre-dose and post-dose during the period including Day 28 | All subjects who received study drug and provided they had sufficient DSM265 and/or DSM450 concentration data for the non-compartmental analysis were included in the pharmacokinetic analysis (all-treated set). | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculum |
|
|
|
| Secondary | DSM265 Pharmacokinetics Profile - AUC 0-∞, AUC 0-168h, and AUC 0-480h | Pre-dose and post-dose during the period including Day 28 for AUC 0-∞, AUC 0-168h, and AUC 0-480h | All subjects who received study drug and provided they had sufficient DSM265 and/or DSM450 concentration data for the non-compartmental analysis were included in the pharmacokinetic analysis (all-treated set). | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculum |
|
|
|
| Secondary | DSM265 Pharmacokinetics Profile - CL/F | Pre-dose and post-dose during the period including Day 28 | All subjects who received study drug and provided they had sufficient DSM265 and/or DSM450 concentration data for the non-compartmental analysis were included in the pharmacokinetic analysis (all-treated set). | Posted | Geometric Mean | Geometric Coefficient of Variation | mL/h | From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculum |
|
|
|
| Secondary | DSM265 Pharmacokinetics Profile - Vz/F | Pre-dose and post-dose during the period including Day 28 | All subjects who received study drug and provided they had sufficient DSM265 and/or DSM450 concentration data for the non-compartmental analysis were included in the pharmacokinetic analysis (all-treated set). | Posted | Geometric Mean | Geometric Coefficient of Variation | mL | From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculum |
|
|
|
| Secondary | DSM450 Pharmacokinetics Profile - T Max | Pre-dose and post-dose during the period including Day 28 | All subjects who received study drug and provided they had sufficient DSM265 and/or DSM450 concentration data for the non-compartmental analysis were included in the pharmacokinetic analysis (all-treated set). | Posted | Median | Full Range | hours | From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculum |
|
|
|
| Secondary | DSM450 Pharmacokinetics Profile - Cmax | Pre-dose and post-dose during the period including Day 28 | All subjects who received study drug and provided they had sufficient DSM265 and/or DSM450 concentration data for the non-compartmental analysis were included in the pharmacokinetic analysis (all-treated set). | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculum |
|
|
|
| Secondary | DSM450 Pharmacokinetics Profile - AUC 0-t, AUC 0-168h, and AUC 0-480h | Pre-dose and post-dose during the period including Day 28 for AUC 0-t, AUC 0-168h, and AUC 0-480h | All subjects who received study drug and provided they had sufficient DSM265 and/or DSM450 concentration data for the non-compartmental analysis were included in the pharmacokinetic analysis (all-treated set). | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculum |
|
|
|
| Secondary | The Pharmacokinetic-pharmacodynamic Profile of Pre-administration of DSM265 on Clearance of Plasmodium Falciparum Parasites After Administration of the Sporozoite Challenge | The profile of plasma concentrations and pharmacokinetic parameters (AUC, Cmax, Tmax, T0-inf, AUC0-t, t1/2) will be reviewed on a background of the safety profile (adverse events, laboratory and ECG data) and the clearance of Plasmodium falciparum parasites (efficacy) after administration of the sporozoite challenge | Data were not collected. Analysis was not done because, because all subjects were administered with the same dose of 400mg DSM; so not enough variability for the "DSM concentration" parameter. | Posted | From first dose of DSM265 (Day -1 in Cohort 1a, Day -7 in Cohort 2 and Day -X in Cohort 3) to 480 hours post-dose |
|
|
| Secondary | Recrudescence of Parasite Kinetics Following DSM265 Administration. | On any re-appearance of parasites, thick smears and PCR samples will be examined to determine whether the parasite is a different variant(recrudescence) or has the same genetic profile as the original infection (re-infection) post-dose | Recrudescence was not observed in this study. | Posted | Day 6 post-inoculum to Day 60 |
|
|
| 0 |
| 5 |
| 1 |
| 5 |
| 5 |
| 5 |
| EG001 | Cohort 1B: Malarone, Sporozoite Challenge | Malarone daily for 9 days from Day -1 to Day 7, sporozoite challenge Day 0 Malarone: 250 mg atovaquone, 100 mg proguanil hydrochloride Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation | 0 | 6 | 0 | 6 | 5 | 6 |
| EG002 | Cohort 2: 400 mg DSM265 (Day-7), Sporozoite Challenge (Day0) | DSM265 400 mg on Day -7, sporozoite challenge on Day 0 DSM265 400 mg: single oral administration in a fed state Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation | 0 | 6 | 0 | 6 | 6 | 6 |
| EG003 | Placebo Cohorts 1A and 2 | Placebo to DSM265 400 mg on Day -7 or Day -1, sporozoite challenge on Day 0 Placebo to DSM265 400 mg: single oral administration in a fed state Plasmodium falciparum sporozoite challenge: Plasmodium falciparum sporozoites (3200) by direct venous inoculation | 0 | 4 | 0 | 4 | 4 | 4 |
|
| Leukopenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Lymphopenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Palpitations | Cardiac disorders | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | Systematic Assessment |
|
| Abdominal Discomfort | Gastrointestinal disorders | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Chills | General disorders | Systematic Assessment |
|
| Fatigue | General disorders | Systematic Assessment |
|
| Pyrexia | General disorders | Systematic Assessment |
|
| Hyperbilirubinaemia | Hepatobiliary disorders | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | Systematic Assessment |
|
| Sinusitis | Infections and infestations | Systematic Assessment |
|
| Viral upper respiratory tract infection | Infections and infestations | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | Systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Dizziness | Nervous system disorders | Systematic Assessment |
|
| Headache | Nervous system disorders | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Dysphonia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
Not provided
Not provided
| D000079426 |
| Vector Borne Diseases |
| AUC 0-168h DBS |
|
| AUC 0-168h Plasma |
|
| AUC 0-480h DBS |
|
| AUC 0-480h Plasma |
|
| AUC 0-168h DBS |
|
| AUC 0-168h Plasma |
|
| AUC 0-480h DBS |
|
| AUC 0-480h Plasma |
|