First-in-Human Trial of Single Ascending Dose, Multiple Ascending Dose and Malaria Challenge Model in Healthy Participants

NCT ID: NCT03261401

Last Updated: 2023-10-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 88 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-15
• Study Completion Date: 2019-06-14

Brief Summary

The primary purpose of this study was to investigate the safety and tolerability of M5717 and to characterize the Pharmacokinetics (PK) /Pharmacodynamic relationship between M5717 PK and parasite clearance in healthy participants following infection with Plasmodium falciparum.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Participants received placebo matched to M5717

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.

Group Type: EXPERIMENTAL

M5717

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

M5717

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

M5717

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

M5717

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

M5717

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

M5717

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

M5717

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

M5717

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

M5717

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

M5717

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

M5717

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

M5717

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

Placebo

Participants received placebo matched to M5717

Intervention Type: DRUG

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 Type: DRUG

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Responsible

Role: STUDY_DIRECTOR

Merck KGaA, Darmstadt, Germany

Locations

Q-Pharm Pty Ltd

Brisbane, , Australia

Countries

Australia

References

McCarthy JS, Yalkinoglu O, Odedra A, Webster R, Oeuvray C, Tappert A, Bezuidenhout D, Giddins MJ, Dhingra SK, Fidock DA, Marquart L, Webb L, Yin X, Khandelwal A, Bagchus WM. Safety, pharmacokinetics, and antimalarial activity of the novel plasmodium eukaryotic translation elongation factor 2 inhibitor M5717: a first-in-human, randomised, placebo-controlled, double-blind, single ascending dose study and volunteer infection study. Lancet Infect Dis. 2021 Dec;21(12):1713-1724. doi: 10.1016/S1473-3099(21)00252-8. Epub 2021 Oct 26.

Reference Type: RESULT

PMID: 34715032 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://clinicaltrials.emdgroup.com/en/trial-details/?id=MS201618_0013

Trial Awareness and Transparency website

https://www.merckgroup.com/en/company/contact-us/medinfo-contact-map.html

Medical Information Location Map - Med Info Contacts

Other Identifiers

203481/Z/16/Z

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

MS201618_0013

Identifier Type: -

Identifier Source: org_study_id