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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03261401
Ethics application status
Date submitted
18/08/2017
Date registered
25/08/2017

Titles & IDs
Public title
First-in-Human Trial of Single Ascending Dose, Multiple Ascending Dose and Malaria Challenge Model in Healthy Participants
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
203481/Z/16/Z
Secondary ID [2] 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 - Placebo
Treatment: Drugs - M5717

Placebo comparator: Part A: Placebo (Pooled) - Participants received capsules containing 50 milligram (mg) of placebo matched similar to M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.

Experimental: Part A: Cohort 1 SAD: M5717 50 mg - Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.

Experimental: Part A: Cohort 2 SAD: M5717 100 mg - Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.

Experimental: Part A: Cohort 3 SAD: M5717 200 mg - Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.

Experimental: Part A: Cohort 4 SAD: M5717 400 mg - Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.

Experimental: Part A: Cohort 5 SAD: M5717 600 mg - Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.

Experimental: Part A: Cohort 6 SAD: M5717 1000 mg - Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.

Experimental: Part A: Cohort 7 SAD: M5717 1250 mg - Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.

Experimental: Part A: Cohort 8 SAD: M5717 1800 mg - Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.

Experimental: Part A: Cohort 9 SAD: M5717 2100 mg - Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.

Experimental: Part C: Challenge Cohort 2 M5717 150 mg - Participants received single oral dose of 150 mg M5717 (eight days after the administration of intravenous malaria inoculum) on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.

Experimental: Part C: Challenge Cohort 1 M5717 400 mg - Participants received single oral dose of 400 mg M5717 (eight days after the administration of intravenous malaria inoculum) on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.

Experimental: Part C: Challenge Cohort 3 M5717 800 mg - Participants received single oral dose of 800 mg M5717 (eight days after the administration of intravenous malaria inoculum) on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.


Treatment: Drugs: M5717
Participants received 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: Placebo
Participants received placebo matched to M5717

Treatment: Drugs: M5717
Participants received single ascending oral dose of M5717 from Part A 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: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation of Study Treatment
Timepoint [1] 0 0
Baseline up to Day 55
Primary outcome [2] 0 0
Part A: Number of Participants With Clinically Significant Changes From Baseline in Laboratory Assessments
Timepoint [2] 0 0
Baseline up to Day 55
Primary outcome [3] 0 0
Part A: Number of Participants With Clinically Significant Changes From Baseline in 12-lead Electrocardiograms (ECGs) Findings
Timepoint [3] 0 0
Baseline up to Day 55
Primary outcome [4] 0 0
Part A: Number of Participants With Clinically Significant Changes From Baseline in Vital Signs
Timepoint [4] 0 0
Baseline up to Day 55
Primary outcome [5] 0 0
Part C: Parasite Reduction Ratio (PRR) Assessed Through Quantitative Polymerase Chain Reaction (qPCR) Analysis
Timepoint [5] 0 0
Day 1 to Day 22
Primary outcome [6] 0 0
Part C: Maximum Observed Plasma Concentration (Cmax) of M5717
Timepoint [6] 0 0
Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dose
Primary outcome [7] 0 0
Part C: Time to Reach Maximum Observed Plasma Concentration (Tmax) of M5717
Timepoint [7] 0 0
Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dose
Primary outcome [8] 0 0
Part C: Terminal Elimination Rate Constant (Lambda z) of M5717
Timepoint [8] 0 0
Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dose
Primary outcome [9] 0 0
Part C: Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of M5717
Timepoint [9] 0 0
Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dose
Primary outcome [10] 0 0
Part C: Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of M5717
Timepoint [10] 0 0
Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dose
Primary outcome [11] 0 0
Part C: Area Under the Plasma Concentration-Time Curve From Time Zero to Time 144 Hours After Drug Administration (AUC0-144h) of M5717
Timepoint [11] 0 0
Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, and 144 hours post-dose
Primary outcome [12] 0 0
Part C: Apparent Terminal Half Life (t1/2) of M5717
Timepoint [12] 0 0
Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dose
Primary outcome [13] 0 0
Part C: Apparent Total Clearance (CL/f) of M5717
Timepoint [13] 0 0
Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dose
Primary outcome [14] 0 0
Part C: Apparent Volume of Distribution During Terminal Phase (VZ/f) of M5717
Timepoint [14] 0 0
Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dose
Primary outcome [15] 0 0
Part C: Time Above or Equal to the Predicted M5717 Minimum Inhibitory Concentration (MIC) of 3 ng/mL (t =>3 ng/mL)
Timepoint [15] 0 0
Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dose
Primary outcome [16] 0 0
Part C: Time Above or Equal to the Predicted M5717 Minimum Parasiticidal Concentration (MPC) of 10 ng/mL (t =>10 ng/mL)
Timepoint [16] 0 0
Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dose
Secondary outcome [1] 0 0
Part A: Maximum Observed Plasma Concentration (Cmax) of M5717
Timepoint [1] 0 0
Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dose
Secondary outcome [2] 0 0
Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of M5717
Timepoint [2] 0 0
Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dose
Secondary outcome [3] 0 0
Part A: Terminal Elimination Rate Constant (Lambda z) of M5717
Timepoint [3] 0 0
Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dose
Secondary outcome [4] 0 0
Part A: Apparent Terminal Half Life (t1/2) of M5717
Timepoint [4] 0 0
Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dose
Secondary outcome [5] 0 0
Part A: Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of M5717
Timepoint [5] 0 0
Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dose
Secondary outcome [6] 0 0
Part A: Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of M5717
Timepoint [6] 0 0
Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dose
Secondary outcome [7] 0 0
Part A: Area Under the Plasma Concentration-Time Curve From Time Zero to Time 144 Hours After Drug Administration (AUC0-144h) of M5717
Timepoint [7] 0 0
Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, and 144 hours post-dose
Secondary outcome [8] 0 0
Part A: Extrapolated Area Under the Plasma Concentration Curve From Time of Last Quantifiable Sample to Infinity (AUCextra%) of M5717
Timepoint [8] 0 0
Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dose
Secondary outcome [9] 0 0
Part A: Apparent Total Clearance (CL/f) of M5717
Timepoint [9] 0 0
Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dose
Secondary outcome [10] 0 0
Part A: Apparent Volume of Distribution During Terminal Phase (VZ/f) of M5717
Timepoint [10] 0 0
Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dose
Secondary outcome [11] 0 0
Part A: Dose Normalized AUC0-inf [AUC(0-inf/Dose)] of M5717
Timepoint [11] 0 0
Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dose
Secondary outcome [12] 0 0
Part A: Dose Normalized AUC0-144h [AUC(0-144hour/Dose)] of M5717
Timepoint [12] 0 0
Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, and 144 hours post-dose
Secondary outcome [13] 0 0
Part A: Dose Normalized AUC0-t [AUC( 0-t/Dose)] of M5717
Timepoint [13] 0 0
Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dose
Secondary outcome [14] 0 0
Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax/Dose) of M5717
Timepoint [14] 0 0
Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dose
Secondary outcome [15] 0 0
Part A: Time Above or Equal to the Predicted M5717 Minimum Inhibitory Concentration (MIC) of 3 ng/mL (t =>3 ng/mL)
Timepoint [15] 0 0
Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dose
Secondary outcome [16] 0 0
Part A: Time Above or Equal to the Predicted M5717 Minimum Parasiticidal Concentration (MPC) of 10 ng/mL (t=>10 ng/mL)
Timepoint [16] 0 0
Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dose
Secondary outcome [17] 0 0
Part C: Parasite Clearance Time
Timepoint [17] 0 0
Day 1 up to Day 22
Secondary outcome [18] 0 0
Part C: Parasite Clearance Half-life (PCT 1/2)
Timepoint [18] 0 0
Day 1 up to Day 22
Secondary outcome [19] 0 0
Part C: Number of Participants With Lag Phase
Timepoint [19] 0 0
Day 1 to Day 22
Secondary outcome [20] 0 0
Part C: Number of Participants With Recrudescence
Timepoint [20] 0 0
Day 1 to Day 22
Secondary outcome [21] 0 0
Part C: Malarial Clinical Score
Timepoint [21] 0 0
Day 1, 2, 3, 4, 5, 6, 7, 9, 11, 13, 15 and 22
Secondary outcome [22] 0 0
Part C: Minimum Inhibitory Concentration (MIC) and Minimum Parasiticidal Concentration at 90% (MPC90)
Timepoint [22] 0 0
Day 1 up to Day 22
Secondary outcome [23] 0 0
Part C: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation of Study Treatment
Timepoint [23] 0 0
Baseline up to Day 44
Secondary outcome [24] 0 0
Part C: Number of Participants With Clinically Significant Changes From Baseline in Laboratory Assessments
Timepoint [24] 0 0
Baseline up to Day 44
Secondary outcome [25] 0 0
Part C: Number of Participants With Clinically Significant Changes From Baseline in 12-lead Electrocardiograms (ECGs) Findings
Timepoint [25] 0 0
Baseline up to Day 44
Secondary outcome [26] 0 0
Part C: Number of Participants With Clinically Significant Changes From Baseline in Vital Signs
Timepoint [26] 0 0
Baseline up to Day 44

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 participant 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
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
* Participants 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.
* Participants 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 participant and/or outcome of the trial.
* Participants who have any history of malaria.
* Participants who have participated in a previous malaria vaccine trial.
* Participants 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
15/09/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
14/06/2019
Sample size
Target
Accrual to date
Final
88
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Q-Pharm Pty Ltd - Brisbane
Recruitment postcode(s) [1] 0 0
- Brisbane

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21


What supporting documents are/will be available?




Results publications and other study-related documents

TypeCitations or Other Details
Journal McCarthy JS, Yalkinoglu O, Odedra A, Webster R, Oe... [More Details]


Results are available at https://clinicaltrials.gov/study/NCT03261401