DSM265 Chemoprophylaxis of Plasmodium Falciparum Malaria
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort 1a: DSM265/placebo, sporozoite inoculum DSM265 400mg / placebo Day -1, sporozoite inoculum Day 0 |
Drug: DSM265 400mg
DSM265 400mg, single oral administration in a fed state
Drug: Placebo to DSM265 400 mg
Placebo to DSM265 400mg, single oral administration in a fed state
Biological: Plasmodium falciparum sporozoite challenge
IV Plasmodium falciparum sporozoites (3200) by direct venous inoculation
Other Names:
|
| Active Comparator: Cohort 1b: Malarone, sporozoite inoculum Malarone daily for 9 days from Day -1 to Day 7, sporozoite inoculum Day 0 |
Biological: Plasmodium falciparum sporozoite challenge
IV Plasmodium falciparum sporozoites (3200) by direct venous inoculation
Other Names:
Drug: Malarone
250 mg atovaquone, 100 mg proguanil hydrochloride
Other Names:
|
| Experimental: Cohort 2: DSM265/placebo, sporozoite inoculum DSM265 400mg / placebo Day -7, sporozoite inoculum Day 0 |
Drug: DSM265 400mg
DSM265 400mg, single oral administration in a fed state
Drug: Placebo to DSM265 400 mg
Placebo to DSM265 400mg, single oral administration in a fed state
Biological: Plasmodium falciparum sporozoite challenge
IV Plasmodium falciparum sporozoites (3200) by direct venous inoculation
Other Names:
|
| Experimental: Cohort 3: DSM265 / placebo, sporozoite inoculum (Optional) DSM265 400mg / placebo Day -X, sporozoite inoculum Day 0 |
Drug: DSM265 400mg
DSM265 400mg, single oral administration in a fed state
Drug: Placebo to DSM265 400 mg
Placebo to DSM265 400mg, single oral administration in a fed state
Biological: Plasmodium falciparum sporozoite challenge
IV Plasmodium falciparum sporozoites (3200) by direct venous inoculation
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Infection Rate [Day 0 to Day 28 post-inoculum (daily)]
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.
- Pre-patent Period [Day 0 to Day 28 post-inoculum (daily)]
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.
Secondary Outcome Measures
- Number of Participants With Adverse Events as a Measure of Safety & Tolerability of DSM265 [From first dose (Day -1 in Cohort 1A and Day -7 in Cohort 2) to Day 60 post-inoculum]
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.
- Number of Participants With Treatment Emergent Adverse Events (TEAE) as a Measure of Safety & Tolerability of Malarone [From first dose (Day -1, Cohort 1b) to Day 60 post-inoculum]
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.
- Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Plasmodium Falciparum Sporozoite Challenge Inoculum [Day 0 to Day 60 post-inoculum]
Safety & tolerability of Plasmodium falciparum sporozoite challenge inoculum during DSM265 administration, and Malarone administration. Measured by adverse events, laboratory data
- DSM265 Pharmacokinetics Profile - T Max [From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculum]
Pre-dose and post-dose during the period including Day 28
- DSM265 Pharmacokinetics Profile - T 1/2 [From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculum]
Pre-dose and post-dose during the period including Day 28
- DSM265 Pharmacokinetics Profile - C Max [From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculum]
Pre-dose and post-dose during the period including Day 28
- DSM265 Pharmacokinetics Profile - 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]
Pre-dose and post-dose during the period including Day 28 for AUC 0-∞, AUC 0-168h, and AUC 0-480h
- DSM265 Pharmacokinetics Profile - CL/F [From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculum]
Pre-dose and post-dose during the period including Day 28
- DSM265 Pharmacokinetics Profile - Vz/F [From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculum]
Pre-dose and post-dose during the period including Day 28
- DSM450 Pharmacokinetics Profile - T Max [From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculum]
Pre-dose and post-dose during the period including Day 28
- DSM450 Pharmacokinetics Profile - Cmax [From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculum]
Pre-dose and post-dose during the period including Day 28
- DSM450 Pharmacokinetics Profile - 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]
Pre-dose and post-dose during the period including Day 28 for AUC 0-t, AUC 0-168h, and AUC 0-480h
- The Pharmacokinetic-pharmacodynamic Profile of Pre-administration of DSM265 on Clearance of Plasmodium Falciparum Parasites 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]
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
- Recrudescence of Parasite Kinetics Following DSM265 Administration. [Day 6 post-inoculum to Day 60]
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
Eligibility Criteria
Criteria
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:
-
Intrauterine device+condoms,
-
Diaphragms+spermicidal gel/foam+condoms,
-
Hormonal contraceptives (oral, depot, patch, injectable or vaginal ring) stabilized for at least 30 days before the study drug + condoms from screening to at least 60 days after dose of DSM265
-
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:
-
Any history of malaria
-
Plans to travel to malaria endemic region during the study period up to last follow up visit or plans to travel outside of Germany during the challenge period
-
unable to be closely followed for social, geographic or psychological reasons
-
Previous participation in any malaria vaccine study or controlled human malaria infection study
-
Participation in any other clinical study within 30 days before enrolment in the study, or plan to participate in another investigational vaccine/drug research during the study period.
-
Woman who is breast-feeding or planning to become pregnant during the study
-
Positive human immunodeficiency virus, seropositive for hepatitis B surface antigen or Hepatitis C virus tests
-
Any confirmed/suspected immunosuppressive or immunodeficient state, including human immunodeficiency virus infection, asplenia, recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the 6 months before enrolment (inhaled and topical steroids are allowed)
-
History of serious psychiatric condition that may affect participation in the study, precludes compliance with the protocol; past or present psychoses; disorder requiring lithium; or within 5 years prior to enrolment, history of a suicide plan or attempt.
-
History of convulsions or severe head trauma
-
Symptoms, physical signs and lab values suggestive of systemic disorders including renal, hepatic, cardiovascular, pulmonary, skin, immunodeficiency, and other conditions which could interfere with the interpretation of the study results or compromise health
-
History of cancer (except basal cell carcinoma of the skin), or diabetes mellitus or of arrhythmias or documented prolonged QTF-interval (>450msec)
-
Clinically significant abnormalities in electrocardiogram at screening: pathologic Q wave, prolonged QT interval, and significant ST-T wave changes, left ventricular hypertrophy, non-sinus rhythm except isolated premature atrial contractions, right or left bundle branch block, advanced A-V heart block (type 2 or type 3)
-
In moderate risk or higher categories for fatal or non-fatal cardiovascular event within 5 years (>10%) determined by non-invasive criteria for cardiac risk
-
Positive family history in relatives <50 years for cardiac disease
-
History of psoriasis or porphyria, which may be exacerbated by chloroquine
-
History of splenectomy
-
Sickle cell anaemia or other red blood cell disorders
-
History of allergy or contra-indications to or having contraindications to the use of chloroquine phosphate, atovaquone-proguanil (cohort 1B), artemether or lumefantrine
-
Use of any prescription drugs (except contraception), herbal supplements or over-the-counter medication in 4 weeks before dosing or 5x half-lives, whichever is longer
-
Use or anticipated use of medications known to cause drug reactions with rescue medications or Malarone, such as cimetidine, metoclopramide, antacids and taken at any point during the study period.
-
Intake of grapefruit, grapefruit juice, Seville orange or other products containing these ingredients within 7 days of the first drug administration
-
Use of chronic immunosuppressive drugs, or other immune modifying drugs within 6 months of enrolment (inhaled and topical corticosteroids and oral anti-histaminic are allowed) and/or during the study period
-
Use of systemic antibiotics with known antimalarial activity within 30 days of study enrolment (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones, or azithromycin ) and/or during the study period
-
Use of immunoglobulins or blood products in 3 months prior to enrolment
-
Suspected/known injecting drug abuse in 5 years preceding enrolment
-
Current smoking more than 10 cigarettes or equivalent per day
-
Plan for major surgery between enrolment and follow up
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Universitätsklinikum Tübingen, Institut für Tropenmedizin | Tübingen | Germany | 72074 |
Sponsors and Collaborators
- Medicines for Malaria Venture
- Institute of Tropical Medicine, University of Tuebingen
Investigators
- Principal Investigator: Benjamin Mordmüller, Dr. med, Institut für Tropenmedizin, Uni. of Tübingen
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- MMV_DSM265_14_01
Study Results
Participant Flow
| Recruitment Details | A total of 40 subjects were screened. Of these 22 (55.0%) were enrolled to participate in the study |
|---|---|
| Pre-assignment Detail | 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. |
| Arm/Group Title | Cohort 1A: 400 mg DSM265, Sporozoite Challenge | Cohort 1B: Malarone, Sporozoite Challenge | Cohort 2: 400 mg DSM265, Sporozoite Challenge | Placebo Cohorts 1A and 2, Sporozoite Challenge |
|---|---|---|---|---|
| Arm/Group Description | 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 | 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 | 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 | 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 |
| Period Title: Overall Study | ||||
| STARTED | 6 | 6 | 6 | 4 |
| COMPLETED | 5 | 6 | 6 | 4 |
| NOT COMPLETED | 1 | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Cohort 1A: 400 mg DSM265, Sporozoite Challenge | Cohort 1B: Malarone, Sporozoite Challenge | Cohort 2: 400 mg DSM265, Sporozoite Challenge | Placebo Cohorts 1A and 2 | Total |
|---|---|---|---|---|---|
| Arm/Group Description | 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 | 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 | 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 | 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 | Total of all reporting groups |
| Overall Participants | 5 | 6 | 6 | 4 | 21 |
| Age, Customized (years) [Mean (Standard Deviation) ] | |||||
| Age (years) |
24.20
(4.02)
|
26.67
(4.93)
|
25.33
(4.18)
|
24.82
(3.95)
|
26.00
(4.24)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
2
40%
|
2
33.3%
|
2
33.3%
|
2
50%
|
8
38.1%
|
| Male |
3
60%
|
4
66.7%
|
4
66.7%
|
2
50%
|
13
61.9%
|
| Race (NIH/OMB) (Count of Participants) | |||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| White |
5
100%
|
6
100%
|
6
100%
|
4
100%
|
21
100%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | |||||
| Germany |
5
100%
|
6
100%
|
6
100%
|
4
100%
|
21
100%
|
Outcome Measures
| Title | Infection Rate |
|---|---|
| Description | 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. |
| Time Frame | Day 0 to Day 28 post-inoculum (daily) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All subjects who received both at least one dose of study medication and the PfSPZ challenge |
| Arm/Group Title | Cohort 1A: 400 mg DSM265 (Day-1), Sporozoite Challenge (Day0) | Cohort 1B: Malarone, Sporozoite Challenge | Cohort 2: 400 mg DSM265 (Day-7), Sporozoite Challenge (Day0) | Placebo Cohorts 1A and 2 |
|---|---|---|---|---|
| Arm/Group Description | 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 | 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 | 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 | 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 |
| Measure Participants | 5 | 6 | 6 | 4 |
| Complete Protection |
5
100%
|
6
100%
|
3
50%
|
0
0%
|
| Parasitemic |
0
0%
|
0
0%
|
3
50%
|
4
100%
|
| Title | Pre-patent Period |
|---|---|
| Description | 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. |
| Time Frame | Day 0 to Day 28 post-inoculum (daily) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All subjects who received both at least one dose of study medication and the PfSPZ challenge |
| Arm/Group Title | Cohort 1A: 400 mg DSM265 (Day-1), Sporozoite Challenge (Day0) | Cohort 1B: Malarone, Sporozoite Challenge | Cohort 2: 400 mg DSM265 (Day-7), Sporozoite Challenge (Day0) | Placebo Cohorts 1A and 2 |
|---|---|---|---|---|
| Arm/Group Description | 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 | 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 | 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 | 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 |
| Measure Participants | 5 | 6 | 6 | 4 |
| Geometric Mean (Geometric Coefficient of Variation) [Days] |
28.0
(0.00)
|
28.0
(0.00)
|
20.6
(2.78)
|
11.7
(7.93)
|
| Title | Number of Participants With Adverse Events as a Measure of Safety & Tolerability of DSM265 |
|---|---|
| Description | 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. |
| Time Frame | From first dose (Day -1 in Cohort 1A and Day -7 in Cohort 2) to Day 60 post-inoculum |
Outcome Measure Data
| Analysis Population Description |
|---|
| All the subjects included in the safety population were administered the study medication. |
| Arm/Group Title | Cohort 1a: DSM265/Placebo, Sporozoite Inoculum | Cohort 2: DSM265/Placebo, Sporozoite Inoculum |
|---|---|---|
| Arm/Group Description | DSM265 400mg / placebo Day -1, sporozoite inoculum Day 0 DSM265 400mg: DSM265 400mg, single oral administration in a fed state Placebo to DSM265 400 mg: Placebo to DSM265 400mg, single oral administration in a fed state Plasmodium falciparum sporozoite challenge: IV Plasmodium falciparum sporozoites (3200) by direct venous inoculation | DSM265 400mg / placebo Day -7, sporozoite inoculum Day 0 DSM265 400mg: DSM265 400mg, single oral administration in a fed state Placebo to DSM265 400 mg: Placebo to DSM265 400mg, single oral administration in a fed state Plasmodium falciparum sporozoite challenge: IV Plasmodium falciparum sporozoites (3200) by direct venous inoculation |
| Measure Participants | 5 | 6 |
| Count of Participants [Participants] |
5
100%
|
6
100%
|
| Title | Number of Participants With Treatment Emergent Adverse Events (TEAE) as a Measure of Safety & Tolerability of Malarone |
|---|---|
| Description | 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. |
| Time Frame | From first dose (Day -1, Cohort 1b) to Day 60 post-inoculum |
Outcome Measure Data
| Analysis Population Description |
|---|
| All the subjects included in the safety population were administered the study medication. |
| Arm/Group Title | Cohort 1B: Malarone, Sporozoite Challenge |
|---|---|
| Arm/Group Description | 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 |
| Measure Participants | 6 |
| Count of Participants [Participants] |
5
100%
|
| Title | Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Plasmodium Falciparum Sporozoite Challenge Inoculum |
|---|---|
| Description | Safety & tolerability of Plasmodium falciparum sporozoite challenge inoculum during DSM265 administration, and Malarone administration. Measured by adverse events, laboratory data |
| Time Frame | Day 0 to Day 60 post-inoculum |
Outcome Measure Data
| Analysis Population Description |
|---|
| All the subjects included in the safety population were administered the study medication. |
| Arm/Group Title | Cohort 1A: 400 mg DSM265 (Day-1), Sporozoite Challenge (Day0) | Cohort 1B: Malarone, Sporozoite Challenge | Cohort 2: 400 mg DSM265 (Day-7), Sporozoite Challenge (Day0) | Placebo Cohorts 1A and 2 |
|---|---|---|---|---|
| Arm/Group Description | 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 | 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 | 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 | 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 |
| Measure Participants | 5 | 6 | 6 | 4 |
| Count of Participants [Participants] |
3
60%
|
5
83.3%
|
5
83.3%
|
4
100%
|
| Title | DSM265 Pharmacokinetics Profile - T Max |
|---|---|
| Description | Pre-dose and post-dose during the period including Day 28 |
| Time Frame | From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculum |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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). |
| Arm/Group Title | Cohort 1A: 400 mg DSM265 (Day-1), Sporozoite Challenge (Day0) | Cohort 2: 400 mg DSM265 (Day-7), Sporozoite Challenge (Day0) |
|---|---|---|
| Arm/Group Description | 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 | 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 |
| Measure Participants | 5 | 6 |
| T max DBS |
2.02
|
8.48
|
| T max Plasma |
2.00
|
8.48
|
| Title | DSM265 Pharmacokinetics Profile - T 1/2 |
|---|---|
| Description | Pre-dose and post-dose during the period including Day 28 |
| Time Frame | From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculum |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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). |
| Arm/Group Title | Cohort 1A: 400 mg DSM265 (Day-1), Sporozoite Challenge (Day0) | Cohort 2: 400 mg DSM265 (Day-7), Sporozoite Challenge (Day0) |
|---|---|---|
| Arm/Group Description | 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 | 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 |
| Measure Participants | 5 | 6 |
| t 1/2 DBS |
132
(31.4)
|
113
(39.0)
|
| t 1/2 Plasma |
134
(34.8)
|
116
(40.4)
|
| Title | DSM265 Pharmacokinetics Profile - C Max |
|---|---|
| Description | Pre-dose and post-dose during the period including Day 28 |
| Time Frame | From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculum |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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). |
| Arm/Group Title | Cohort 1A: 400 mg DSM265 (Day-1), Sporozoite Challenge (Day0) | Cohort 2: 400 mg DSM265 (Day-7), Sporozoite Challenge (Day0) |
|---|---|---|
| Arm/Group Description | 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 | 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 |
| Measure Participants | 5 | 6 |
| C max DBS |
6860
(28.2)
|
6990
(15.0)
|
| C max Plasma |
13300
(34.3)
|
11200
(18.0)
|
| Title | DSM265 Pharmacokinetics Profile - AUC 0-∞, AUC 0-168h, and AUC 0-480h |
|---|---|
| Description | Pre-dose and post-dose during the period including Day 28 for AUC 0-∞, AUC 0-168h, and AUC 0-480h |
| Time Frame | From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculum |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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). |
| Arm/Group Title | Cohort 1A: 400 mg DSM265 (Day-1), Sporozoite Challenge (Day0) | Cohort 2: 400 mg DSM265 (Day-7), Sporozoite Challenge (Day0) |
|---|---|---|
| Arm/Group Description | 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 | 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 |
| Measure Participants | 5 | 6 |
| AUC 0-∞ DBS |
979000
(25.8)
|
906000
(29.8)
|
| AUC 0-∞ Plasma |
1870000
(23.4)
|
1540000
(30.4)
|
| AUC 0-168h DBS |
582000
(22.8)
|
568000
(13.3)
|
| AUC 0-168h Plasma |
1100000
(22.3)
|
949000
(14.0)
|
| AUC 0-480h DBS |
863000
(22.0)
|
847000
(25.4)
|
| AUC 0-480h Plasma |
1680000
(19.5)
|
1430000
(25.9)
|
| Title | DSM265 Pharmacokinetics Profile - CL/F |
|---|---|
| Description | Pre-dose and post-dose during the period including Day 28 |
| Time Frame | From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculum |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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). |
| Arm/Group Title | Cohort 1A: 400 mg DSM265 (Day-1), Sporozoite Challenge (Day0) | Cohort 2: 400 mg DSM265 (Day-7), Sporozoite Challenge (Day0) |
|---|---|---|
| Arm/Group Description | 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 | 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 |
| Measure Participants | 5 | 6 |
| CL/F DBS |
409
(25.8)
|
441
(29.8)
|
| CL/F Plasma |
214
(23.4)
|
260
(30.4)
|
| Title | DSM265 Pharmacokinetics Profile - Vz/F |
|---|---|
| Description | Pre-dose and post-dose during the period including Day 28 |
| Time Frame | From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculum |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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). |
| Arm/Group Title | Cohort 1A: 400 mg DSM265 (Day-1), Sporozoite Challenge (Day0) | Cohort 2: 400 mg DSM265 (Day-7), Sporozoite Challenge (Day0) |
|---|---|---|
| Arm/Group Description | 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 | 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 |
| Measure Participants | 5 | 6 |
| Vz/F DBS |
77900
(29.0)
|
71700
(18.7)
|
| Vz/F Plasma |
41400
(31.8)
|
43600
(18.9)
|
| Title | DSM450 Pharmacokinetics Profile - T Max |
|---|---|
| Description | Pre-dose and post-dose during the period including Day 28 |
| Time Frame | From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculum |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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). |
| Arm/Group Title | Cohort 1A: 400 mg DSM265 (Day-1), Sporozoite Challenge (Day0) | Cohort 2: 400 mg DSM265 (Day-7), Sporozoite Challenge (Day0) |
|---|---|---|
| Arm/Group Description | 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 | 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 |
| Measure Participants | 5 | 6 |
| t max DBS |
169
|
216
|
| t max Plasma |
169
|
169
|
| Title | DSM450 Pharmacokinetics Profile - Cmax |
|---|---|
| Description | Pre-dose and post-dose during the period including Day 28 |
| Time Frame | From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculum |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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). |
| Arm/Group Title | Cohort 1A: 400 mg DSM265 (Day-1), Sporozoite Challenge (Day0) | Cohort 2: 400 mg DSM265 (Day-7), Sporozoite Challenge (Day0) |
|---|---|---|
| Arm/Group Description | 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 | 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 |
| Measure Participants | 5 | 6 |
| Cmax DBS |
545
(35.3)
|
714
(37.1)
|
| Cmax Plasma |
999
(31.0)
|
1170
(36.7)
|
| Title | DSM450 Pharmacokinetics Profile - AUC 0-t, AUC 0-168h, and AUC 0-480h |
|---|---|
| Description | Pre-dose and post-dose during the period including Day 28 for AUC 0-t, AUC 0-168h, and AUC 0-480h |
| Time Frame | From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculum |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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). |
| Arm/Group Title | Cohort 1A: 400 mg DSM265 (Day-1), Sporozoite Challenge (Day0) | Cohort 2: 400 mg DSM265 (Day-7), Sporozoite Challenge (Day0) |
|---|---|---|
| Arm/Group Description | 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 | 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 |
| Measure Participants | 5 | 6 |
| AUC 0-∞ DBS |
185000
(34.9)
|
225000
(42.5)
|
| AUC 0-∞ Plasma |
326000
(32.1)
|
367000
(39.7)
|
| AUC 0-168h DBS |
63800
(44.9)
|
85300
(45.1)
|
| AUC 0-168h Plasma |
115000
(45.9)
|
142000
(40.4)
|
| AUC 0-480h DBS |
185000
(34.9)
|
234000
(46.5)
|
| AUC 0-480h Plasma |
326000
(32.1)
|
375000
(44.1)
|
| Title | The Pharmacokinetic-pharmacodynamic Profile of Pre-administration of DSM265 on Clearance of Plasmodium Falciparum Parasites After Administration of the Sporozoite Challenge |
|---|---|
| Description | 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 |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Cohort 1A: 400 mg DSM265 (Day-1), Sporozoite Challenge (Day0) | Cohort 2: 400 mg DSM265 (Day-7), Sporozoite Challenge (Day0) |
|---|---|---|
| Arm/Group Description | 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 | 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 |
| Measure Participants | 0 | 0 |
| Title | Recrudescence of Parasite Kinetics Following DSM265 Administration. |
|---|---|
| Description | 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 |
| Time Frame | Day 6 post-inoculum to Day 60 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Recrudescence was not observed in this study. |
| Arm/Group Title | Cohort 1A: 400 mg DSM265 (Day-1), Sporozoite Challenge (Day0) | Cohort 2: 400 mg DSM265 (Day-7), Sporozoite Challenge (Day0) |
|---|---|---|
| Arm/Group Description | 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 | 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 |
| Measure Participants | 0 | 0 |
Adverse Events
| Time Frame | 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 | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | Cohort 1A: 400 mg DSM265 (Day-1), Sporozoite Challenge (Day0) | Cohort 1B: Malarone, Sporozoite Challenge | Cohort 2: 400 mg DSM265 (Day-7), Sporozoite Challenge (Day0) | Placebo Cohorts 1A and 2 | ||||
| Arm/Group Description | 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 | 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 | 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 | 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 | ||||
All Cause Mortality |
||||||||
| Cohort 1A: 400 mg DSM265 (Day-1), Sporozoite Challenge (Day0) | Cohort 1B: Malarone, Sporozoite Challenge | Cohort 2: 400 mg DSM265 (Day-7), Sporozoite Challenge (Day0) | Placebo Cohorts 1A and 2 | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
Serious Adverse Events |
||||||||
| Cohort 1A: 400 mg DSM265 (Day-1), Sporozoite Challenge (Day0) | Cohort 1B: Malarone, Sporozoite Challenge | Cohort 2: 400 mg DSM265 (Day-7), Sporozoite Challenge (Day0) | Placebo Cohorts 1A and 2 | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/5 (20%) | 0/6 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Vascular disorders | ||||||||
| Pulmonary embolism | 1/5 (20%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||
| Cohort 1A: 400 mg DSM265 (Day-1), Sporozoite Challenge (Day0) | Cohort 1B: Malarone, Sporozoite Challenge | Cohort 2: 400 mg DSM265 (Day-7), Sporozoite Challenge (Day0) | Placebo Cohorts 1A and 2 | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/5 (100%) | 5/6 (83.3%) | 6/6 (100%) | 4/4 (100%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Haemolysis | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 1/4 (25%) | 1 |
| Leukopenia | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 1/4 (25%) | 1 |
| Lymphopenia | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 2/6 (33.3%) | 3 | 0/4 (0%) | 0 |
| Cardiac disorders | ||||||||
| Palpitations | 1/5 (20%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/4 (25%) | 4 |
| Tachycardia | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 4/6 (66.7%) | 5 | 2/4 (50%) | 2 |
| Gastrointestinal disorders | ||||||||
| Abdominal Discomfort | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/4 (50%) | 2 |
| Nausea | 0/5 (0%) | 0 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 1/4 (25%) | 1 |
| General disorders | ||||||||
| Chills | 0/5 (0%) | 0 | 1/6 (16.7%) | 1 | 3/6 (50%) | 3 | 2/4 (50%) | 2 |
| Fatigue | 1/5 (20%) | 1 | 1/6 (16.7%) | 1 | 6/6 (100%) | 10 | 4/4 (100%) | 7 |
| Pyrexia | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 3/6 (50%) | 8 | 2/4 (50%) | 6 |
| Hepatobiliary disorders | ||||||||
| Hyperbilirubinaemia | 1/5 (20%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Infections and infestations | ||||||||
| Nasopharyngitis | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 1/4 (25%) | 1 |
| Sinusitis | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 | 1/4 (25%) | 1 |
| Viral upper respiratory tract infection | 1/5 (20%) | 1 | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Investigations | ||||||||
| Alanine aminotransferase increased | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 | 0/4 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||
| Hyperkalaemia | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 | 0/4 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Myalgia | 1/5 (20%) | 1 | 0/6 (0%) | 0 | 4/6 (66.7%) | 4 | 2/4 (50%) | 3 |
| Nervous system disorders | ||||||||
| Dizziness | 1/5 (20%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 3/4 (75%) | 4 |
| Headache | 1/5 (20%) | 2 | 1/6 (16.7%) | 1 | 5/6 (83.3%) | 11 | 4/4 (100%) | 11 |
| Psychiatric disorders | ||||||||
| Insomnia | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/4 (50%) | 2 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Cough | 1/5 (20%) | 1 | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 | 1/4 (25%) | 1 |
| Dysphonia | 0/5 (0%) | 0 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Dyspnoea | 1/5 (20%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 1/4 (25%) | 1 |
| Nasal congestion | 0/5 (0%) | 0 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Oropharyngeal pain | 1/5 (20%) | 1 | 2/6 (33.3%) | 2 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||
| Hyperhidrosis | 0/5 (0%) | 0 | 1/6 (16.7%) | 2 | 3/6 (50%) | 3 | 1/4 (25%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Jörg Möhrle |
|---|---|
| Organization | Medicines for Malaria Venture |
| Phone | +41 22 555 0330 |
| moehrlej@mmv.org |
- MMV_DSM265_14_01