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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03261401




Registration number
NCT03261401
Ethics application status
Date submitted
18/08/2017
Date registered
25/08/2017
Date last updated
19/06/2019

Titles & IDs
Public title
First-in-Human Trial of Single Ascending Dose, Multiple Ascending Dose and Malaria Challenge Model in Healthy Subjects
Scientific title
A Phase I, First-in-Human, Randomized, Double-Blind, Placebo-Controlled Trial of Single and Multiple Ascending Doses of M5717 to Assess the Safety, Tolerability and Pharmacokinetic Profile of Oral Doses, and to Assess the Antimalarial Activity of M5717 Against Plasmodium Falciparum in Healthy Male and Female Adult Subjects
Secondary ID [1] 0 0
MS201618_0013
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Healthy 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - M5717
Treatment: Drugs - M5717
Treatment: Drugs - Placebo
Treatment: Drugs - M5717

Experimental: Part A: M5717 -

Placebo Comparator: Part A: Placebo -

Experimental: Part B: M5717 -

Placebo Comparator: Part B: Placebo -

Experimental: Part C: M5717 -


Treatment: Drugs: M5717
Subjects will receive single ascending oral dose of M5717 after at least 8 hours of fasting together with water on Day 1, followed by a 4-hour post-dose fast

Treatment: Drugs: M5717
Subjects will receive multiple ascending oral doses of M5717 after an overnight fast of at least 8 hours once daily for 3 days, followed by a 4-hour post-dose fast

Treatment: Drugs: Placebo
Subjects will receive placebo matched to M5717

Treatment: Drugs: M5717
Subjects will receive single ascending oral dose of M5717 from Part A or as applicable multiple ascending oral doses of M5717 from Part B after at least 8 hours of fasting together with water on Day 1, followed by a 4-hour post-dose fast

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part A and Part B: Occurrence and Severity of Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Timepoint [1] 0 0
Day 1 up to end of trial visit (Week 7)
Primary outcome [2] 0 0
Part A and Part B: Occurrence of Clinically Significant Changes and Abnormalities From Baseline in Vital Signs, Laboratory Parameters and 12-lead Electrocardiogram (ECG) Findings
Timepoint [2] 0 0
Day 1 up to end of trial visit (Week 7)
Primary outcome [3] 0 0
Part C: Parasite Reduction Ratio (PRR) Assessed Through Quantitative Polymerase Chain Reaction (qPCR) Analysis
Timepoint [3] 0 0
Day 1 to Week 4 (Day 22)
Primary outcome [4] 0 0
Part C: Maximum Observed Blood Concentration (Cmax) of M5717
Timepoint [4] 0 0
Pre-dose up to end of trial visit (Week 7)
Primary outcome [5] 0 0
Part C: Time to Reach Maximum Blood Concentration of M5717
Timepoint [5] 0 0
Pre-dose up to end of trial visit (Week 7)
Primary outcome [6] 0 0
Part C: Elimination Rate Constant (?z)
Timepoint [6] 0 0
Pre-dose up to end of trial visit (Week 7)
Primary outcome [7] 0 0
Part C: Apparent Terminal Half-Life (1/2)
Timepoint [7] 0 0
Pre-dose up to end of trial visit (Week 7)
Primary outcome [8] 0 0
Part C: Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M5717
Timepoint [8] 0 0
Pre-dose up to end of trial visit (Week 7)
Primary outcome [9] 0 0
Part C: Area Under the Blood Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of M5717
Timepoint [9] 0 0
Pre-dose up to end of trial visit (Week 7)
Primary outcome [10] 0 0
Part C: Area Under the Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of M5717
Timepoint [10] 0 0
Pre-dose up to end of trial visit (Week 7)
Primary outcome [11] 0 0
Part C: Area Under the Concentration-Time Curve From Time Zero to 144 Hours (AUC0-144) of M5717
Timepoint [11] 0 0
Pre-dose up to end of trial visit (Week 7)
Primary outcome [12] 0 0
Part C: Area Under the Concentration-Time Curve From Time tlast Extrapolated to Infinity (AUCextra%) of M5717
Timepoint [12] 0 0
Pre-dose up to end of trial visit (Week 7)
Primary outcome [13] 0 0
Part C: Total Body Clearance (CL/f) of M5717
Timepoint [13] 0 0
Pre-dose up to end of trial visit (Week 7)
Primary outcome [14] 0 0
Part C: Apparent Volume of Distribution (Vz/f) of M5717
Timepoint [14] 0 0
Pre-dose up to end of trial visit (Week 7)
Primary outcome [15] 0 0
Part C: Dose Normalized Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M5717
Timepoint [15] 0 0
Pre-dose up to end of trial visit (Week 7)
Primary outcome [16] 0 0
Part C: Dose Normalized Area Under the Blood Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t) of M5717
Timepoint [16] 0 0
Pre-dose up to end of trial visit (Week 7)
Primary outcome [17] 0 0
Part C: Dose Normalized Maximum Observed Blood Concentration (Cmax) of M5717
Timepoint [17] 0 0
Pre-dose up to end of trial visit (Week 7)
Primary outcome [18] 0 0
Part C: Time Above or Equal to the Predicted M5717 Mouse Minimal Parasiticidal Concentration (MPC) of 10 nanogram per milliliter
Timepoint [18] 0 0
Pre-dose up to end of trial visit (Week 7)
Primary outcome [19] 0 0
Part C: Time Above or Equal to the Predicted M5717 Mouse Minimal Parasiticidal Concentration (MPC) of 3 nanogram per milliliter
Timepoint [19] 0 0
Pre-dose up to end of trial visit (Week 7)
Primary outcome [20] 0 0
Part C: Accumulation ratio for AUC 0-24 of M5717
Timepoint [20] 0 0
Pre-dose up to end of trial visit (Week 7)
Primary outcome [21] 0 0
Part C: Accumulation Ratio for Cmax of M5717
Timepoint [21] 0 0
Pre-dose up to end of trial visit (Week 7)
Primary outcome [22] 0 0
Part C: Area Under the Concentration-Time Curve Over Entire Dosing Time Period From Time Zero to Last Sampling Time (AUC 0-t,overall)
Timepoint [22] 0 0
Pre-dose up to end of trial visit (Week 7)
Primary outcome [23] 0 0
Part C: Area Under the Concentration-Time Curve Over Entire Dosing Time Period (From Time Zero Extrapolated to Infinity (AUC 0-inf,overall)
Timepoint [23] 0 0
Pre-dose up to end of trial visit (Week 7)
Primary outcome [24] 0 0
Part C: Average Blood Concentration at Steady State (Cav)
Timepoint [24] 0 0
Pre-dose up to end of trial visit (Week 7)
Primary outcome [25] 0 0
Part C: Minimum Observed Blood Concentration (Cmin)
Timepoint [25] 0 0
Pre-dose up to end of trial visit (Week 7)
Secondary outcome [1] 0 0
Part A: Maximum Observed Blood Concentration (Cmax) of M5717
Timepoint [1] 0 0
Pre-dose up to end of trial visit (Week 7)
Secondary outcome [2] 0 0
Part A: Time to Reach Maximum Blood Concentration (tmax) of M5717
Timepoint [2] 0 0
Pre-dose up to end of trial visit (Week 7)
Secondary outcome [3] 0 0
Part A: Apparent Terminal Half-Life (t1/2)
Timepoint [3] 0 0
Pre-dose up to end of trial visit (Week 7)
Secondary outcome [4] 0 0
Part A: Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M5717
Timepoint [4] 0 0
Pre-dose up to end of trial visit (Week 7)
Secondary outcome [5] 0 0
Part A: Area Under the Blood Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of M5717
Timepoint [5] 0 0
Pre-dose up to end of trial visit (Week 7)
Secondary outcome [6] 0 0
Part A: Area Under the Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of M5717
Timepoint [6] 0 0
Pre-dose up to end of trial visit (Week 7)
Secondary outcome [7] 0 0
Part A: Area Under the Concentration-Time Curve From Time Zero to 144 Hours (AUC0-144) of M5717
Timepoint [7] 0 0
Pre-dose up to end of trial visit (Week 7)
Secondary outcome [8] 0 0
Part A: Area Under the Concentration-Time Curve From Time tlast Extrapolated to Infinity (AUCextra%) of M5717
Timepoint [8] 0 0
Pre-dose up to end of trial visit (Week 7)
Secondary outcome [9] 0 0
Part A: Total Body Clearance (CL/f) of M5717
Timepoint [9] 0 0
Pre-dose up to end of trial visit (Week 7)
Secondary outcome [10] 0 0
Part A: Apparent Volume of Distribution (Vz/f) of M5717
Timepoint [10] 0 0
Pre-dose up to end of trial visit (Week 7)
Secondary outcome [11] 0 0
Part A: Dose Normalized Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M5717
Timepoint [11] 0 0
Pre-dose up to end of trial visit (Week 7)
Secondary outcome [12] 0 0
Part A: Dose Normalized Area Under the Blood Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t) of M5717
Timepoint [12] 0 0
Pre-dose up to end of trial visit (Week 7)
Secondary outcome [13] 0 0
Part A: Dose Normalized Maximum Observed Blood Concentration (Cmax) of M5717
Timepoint [13] 0 0
Pre-dose up to end of trial visit (Week 7)
Secondary outcome [14] 0 0
Part A: Time Above or Equal to the Predicted M5717 Mouse Minimal Parasiticidal Concentration (MPC) of 10 nanogram per milliliter
Timepoint [14] 0 0
Pre-dose up to end of trial visit (Week 7)
Secondary outcome [15] 0 0
Part A: Time Above or Equal to the Predicted M5717 Mouse Minimal Parasiticidal Concentration (MPC) of 3 nanogram per milliliter
Timepoint [15] 0 0
Pre-dose up to end of trial visit (Week 7)
Secondary outcome [16] 0 0
Part B: Maximum Observed Blood Concentration (Cmax) of M5717
Timepoint [16] 0 0
Pre-dose up to end of trial visit (Week 7)
Secondary outcome [17] 0 0
Part B: Time to Reach Maximum Blood Concentration (tmax) of M5717
Timepoint [17] 0 0
Pre-dose up to end of trial visit (Week 7)
Secondary outcome [18] 0 0
Part B: Area Under the Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of M5717
Timepoint [18] 0 0
Pre-dose up to end of trial visit (Week 7)
Secondary outcome [19] 0 0
Part B: Area Under the Blood Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of M5717
Timepoint [19] 0 0
Pre-dose up to end of trial visit (Week 7)
Secondary outcome [20] 0 0
Part B: Dose Normalized Area Under the Blood Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t) of M5717
Timepoint [20] 0 0
Pre-dose up to end of trial visit (Week 7)
Secondary outcome [21] 0 0
Part B: Dose Normalized Maximum Observed Blood Concentration (Cmax) of M5717
Timepoint [21] 0 0
Pre-dose up to end of trial visit (Week 7)
Secondary outcome [22] 0 0
Part B: Area Under the Concentration-Time Curve From Time Zero to 144 Hours (AUC0-144) of M5717
Timepoint [22] 0 0
Pre-dose up to end of trial visit (Week 7)
Secondary outcome [23] 0 0
Part B: Elimination Rate Constant (?z)
Timepoint [23] 0 0
Pre-dose up to end of trial visit (Week 7)
Secondary outcome [24] 0 0
Part B: Apparent Terminal Half-Life (t1/2)
Timepoint [24] 0 0
Pre-dose up to end of trial visit (Week 7)
Secondary outcome [25] 0 0
Part B: Accumulation Ratio for AUC 0-24 (R acc AUC) of M5717
Timepoint [25] 0 0
Pre-dose up to end of trial visit (Week 7)
Secondary outcome [26] 0 0
Part B: Accumulation ratio for C max (R acc Cmax)
Timepoint [26] 0 0
Pre-dose up to end of trial visit (Week 7)
Secondary outcome [27] 0 0
Part B: Area Under the Concentration-Time Curve Over Entire Dosing Time Period From Time Zero to Last Sampling Time (AUC 0-t,overall)
Timepoint [27] 0 0
Pre-dose up to end of trial visit (Week 7)
Secondary outcome [28] 0 0
Part B: Area Under the Concentration-Time Curve Over Entire Dosing Time Period (From Time Zero Extrapolated to Infinity (AUC 0-inf,overall)
Timepoint [28] 0 0
Pre-dose up to end of trial visit (Week 7)
Secondary outcome [29] 0 0
Part B: Time Above or Equal to the Predicted M5717 Mouse Minimal Parasiticidal Concentration (MPC) of 10 nanogram per milliliter
Timepoint [29] 0 0
Pre-dose up to end of trial visit (Week 7)
Secondary outcome [30] 0 0
Part B: Time Above or Equal to the Predicted M5717 Mouse Minimal Parasiticidal Concentration (MPC) of 3 nanogram per milliliter
Timepoint [30] 0 0
Pre-dose up to end of trial visit (Week 7)
Secondary outcome [31] 0 0
Part B: Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M5717
Timepoint [31] 0 0
Pre-dose up to end of trial visit (Week 7)
Secondary outcome [32] 0 0
Part B: Dose Normalized Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M5717
Timepoint [32] 0 0
Pre-dose up to end of trial visit (Week 7)
Secondary outcome [33] 0 0
Part B: Area Under the Curve From Time tlast Extrapolated to Infinity Given as Percentage of AUC 0-infinity (AUC extra%)
Timepoint [33] 0 0
Pre-dose up to end of trial visit (Week 7)
Secondary outcome [34] 0 0
Part B: Total Body Clearance (CL/f) of M5717
Timepoint [34] 0 0
Pre-dose up to end of trial visit (Week 7)
Secondary outcome [35] 0 0
Part B: Apparent Volume of Distribution (Vz/f) of M5717
Timepoint [35] 0 0
Pre-dose up to end of trial visit (Week 7)
Secondary outcome [36] 0 0
Part B: Average Blood Concentration at Steady State (Cav)
Timepoint [36] 0 0
Pre-dose up to end of trial visit (Week 7)
Secondary outcome [37] 0 0
Part B: Minimum Observed Blood Concentration (Cmin)
Timepoint [37] 0 0
Pre-dose up to end of trial visit (Week 7)
Secondary outcome [38] 0 0
Parasite Clearance Time
Timepoint [38] 0 0
Day 1 up to Week 4 (Day 22)
Secondary outcome [39] 0 0
Minimal Inhibitory Concentration
Timepoint [39] 0 0
Day 1 up to Week 4 (Day 22)
Secondary outcome [40] 0 0
Lag Phase Assessed by Steady Exponential Decline in Parasite Count - Lag phase is defined as the time period (measured in hours) between administration of the test drug to a parasite infected subject until first sign of parasiticidal effect in terms of steady exponential decline in the parasite count.
Timepoint [40] 0 0
Day 1 up to Week 4 (Day 22)
Secondary outcome [41] 0 0
Number of Subjects With Recrudescence
Timepoint [41] 0 0
Day 1 up to Week 4 (Day 22)
Secondary outcome [42] 0 0
Malarial Clinical Score
Timepoint [42] 0 0
Day 1 up to Week 4 (Day 22)
Secondary outcome [43] 0 0
Part C: Occurrence of Treatment-emergent Adverse Events (TEAEs) and Serious AEs (SAEs)
Timepoint [43] 0 0
Day 1 up to end of trial visit (Week 7)
Secondary outcome [44] 0 0
Part C: Occurrence of TEAEs and SAEs by Severity
Timepoint [44] 0 0
Day 1 up to end of trial visit (Week 7)
Secondary outcome [45] 0 0
Part C: Occurrence of Clinically Significant Changes and Abnormalities From Baseline in Vital Signs, Laboratory Parameters and 12-lead Electrocardiogram (ECG) Findings
Timepoint [45] 0 0
Day 1 up to end of trial visit (Week 7)
Secondary outcome [46] 0 0
Part A: Elimination Rate Constant (?z)
Timepoint [46] 0 0
Pre-dose up to end of trial visit (Week 7)
Secondary outcome [47] 0 0
Minimal Parasiticidal Concentration (MPC)
Timepoint [47] 0 0
Day 1 up to Week 4 (Day 22)
Secondary outcome [48] 0 0
Parasite Clearance Half-life (PCt½) - The parasite clearance half-life, defined as the time needed for parasitemia to be reduced by half during the log-linear phase of parasite clearance.
Timepoint [48] 0 0
Day 1 up to Week 4 (Day 22)

Eligibility
Key inclusion criteria
- Adult men and women of non-childbearing potential, with total body weight greater than
or equal to 50.0 kilogram and body mass index (BMI) between 19.0 kilogram per meter
square(kg/m^2) and 29.9 kg/m^2.

- Healthy as assessed by the Investigator with no clinically significant abnormality
identified on physical examination or laboratory evaluation and no active clinically
significant disorder, condition, infection or disease that would pose a risk to
subject safety or interfere with the trial evaluation, procedures, or completion.

- Other protocol defined inclusion criteria could apply.
Minimum age
18 Years
Maximum age
55 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- Subjects with history or presence of clinically relevant respiratory,
gastrointestinal, renal, hepatic, hematological, lymphatic, neurological,
cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological
dermatological, connective tissue diseases or disorders.

- Subjects with history of relevant drug hypersensitivity, ascertained or presumptive
allergy/hypersensitivity to the active drug substance and/or formulation ingredients;
history of serious allergic reactions leading to hospitalization or any other allergic
reaction in general, which the Investigator considers may affect the safety of the
subject and/or outcome of the trial.

- Subjects who have any history of malaria.

- Subjects who have participated in a previous malaria vaccine trial.

- Subjects who have participated in a previous human malaria challenge trial.

Study design
Purpose of the study
Other
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Q-Pharm Pty Ltd - Brisbane
Recruitment postcode(s) [1] 0 0
4006 - Brisbane

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Merck KGaA, Darmstadt, Germany
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The primary purpose of this study is to investigate the safety and tolerability of M5717 and
to characterize the Pharmacokinetics /Pharmacodynamic relationship between M5717 PK and
parasite clearance in healthy subjects following infection with Plasmodium falciparum.
Trial website
https://clinicaltrials.gov/show/NCT03261401
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Responsible
Address 0 0
Merck KGaA, Darmstadt, Germany
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications