Malaria
Conditions
Brief summary
The purpose of this study is to assess the antimalarial activity, pharmacokinetics, and safety of MK-7602 in healthy adults following Plasmodium falciparum (P. falciparum) infection.
Interventions
OTHERPlasmodium falciparum
Parasite inoculation administered by intravenous (IV) infusion as the challenge agent
DRUGMK-7602
Capsules to be administered orally.
Tablets to be administered orally as definitive antimalarial treatment.
DRUGPrimaquine
Tablets to be administered orally as definitive antimalarial treatment.
DRUGArtesunate
Intravenous (IV) infusion to be administered as definitive antimalarial treatment.
Tablets to be administered orally as definitive antimalarial treatment.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
The main inclusion and
Exclusion criteria
include but are not limited to the following: Inclusion Criteria: * Is in good health * Has a body mass index (BMI) between 18 and 32 kg/m2, inclusive * For participant assigned male sex at birth: If capable of producing sperm, participant must agree to the following during the study treatment period and for at least 90 days after the last dose of MK-7602: Refrain from donating sperm, plus EITHER be abstinent OR must agree to use male condom plus additional contraceptive method * For participant assigned female sex at birth: EITHER be a person of nonchildbearing potential (PONCBP) OR must use a highly effective contraceptive method or be abstinent during the intervention period and for at least 10 days after the last dose of study intervention * Must provide confirmation of not living alone (at any stage from inoculation day until the end of the study). A participant who lives alone may be included on a case-by-case basis. * Agrees to refrain from eating food containing poppy seeds for 48 hours prior to screening, malaria inoculation, and MK-7602 administration
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 2 Multiple dose: Elimination Half-life (t1/2) of MK-7602 | Pre-dose of MK-7602 on Day 8 and post-first dose of MK-7602 at 0.5, 1, 2, 3, 4, 8, 12, 24, 30, 36, 48, 54, 60, 72, 78, 84 and 96 hours and then once daily on Days 13, 15, 17, 20, and 22 | Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine the t½ for Part 2. |
| Part 2 Multiple dose: Maximum Plasma Concentration (Cmax) of MK-7602 | Pre-dose of MK-7602 on Day 8 and post-first dose of MK-7602 at 0.5, 1, 2, 3, 4, 8, 12, 24, 30, 36, 48, 54, 60, 72, 78, 84 and 96 hours and then once daily on Days 13, 15, 17, 20, and 22 | Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine the Cmax for Part 2. |
| Part 2 Multiple dose: Time to Maximum Plasma Concentration (Tmax) of MK-7602 | Pre-dose of MK-7602 on Day 8 and post-first dose of MK-7602 at 0.5, 1, 2, 3, 4, 8, 12, 24, 30, 36, 48, 54, 60, 72, 78, 84 and 96 hours and then once daily on Days 13, 15, 17, 20, and 22 | Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine the Tmax for Part 2. |
| Parasite reduction ratio (PRR48) (Parts 1 and 2) | Pre-inoculation on Day 0, once daily Days 4 to 7, pre-dose of MK-7602 on Day 8, post-first dose of MK-7602 at 2, 4, 8, 12, 16, 24, 30, 36, 48, 54, 60, 72, (78 Part 2 only), 84, and 96 hours, and once daily Days 13, 15, 17, 20, 22, 24, 27, 29, 31, and 34 | PRR48 is the logarithm of the parasite reduction ratio per 48 hours determined from parasitemia data from time 0 to time 48 hours. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine the PRR48. |
| Parasite Clearance Half-life (PCt1/2) (Parts 1 and 2) | Pre-inoculation on Day 0, once daily Days 4 to 7, pre-dose of MK-7602 on Day 8, post-first dose of MK-7602 at 2, 4, 8, 12, 16, 24, 30, 36, 48, 54, 60, 72, (78 Part 2 only), 84, and 96 hours, and once daily Days 13, 15, 17, 20, 22, 24, 27, 29, 31, and 34 | PCt1/2 is the half-life of the log-linear portion of the parasite clearance curve. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine the PCt1/2. |
| Parasite Regrowth (Parts 1 and 2) | Pre-inoculation on Day 0, once daily Days 4 to 7, pre-dose of MK-7602 on Day 8, post-first dose of MK-7602 at 2, 4, 8, 12, 16, 24, 30, 36, 48, 54, 60, 72, (78 Part 2 only), 84, and 96 hours, and once daily Days 13, 15, 17, 20, 22, 24, 27, 29, 31, and 34 | Parasite regrowth is defined as initial parasite clearance followed by asexual parasite regrowth above 5,000 parasites/mL. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine the parasite regrowth. |
| Part 1 Single dose: Area Under the Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of MK-7602 | Pre-dose of MK-7602 on Day 8 and post-dose of MK-7602 at 0.5, 1, 2, 3, 4, 8, 12, 24, 30, 36, 48, 54, 60, 72 and 96 hours and then once daily on Days 13, 15, 17, 20, and 22 | Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine the AUC0-inf for Part 1. |
| Part 1 Single dose: Maximum Plasma Concentration (Cmax) of MK-7602 | Pre-dose of MK-7602 on Day 8 and post-dose of MK-7602 at 0.5, 1, 2, 3, 4, 8, 12, 24, 30, 36, 48, 54, 60, 72 and 96 hours and then once daily on Days 13, 15, 17, 20, and 22 | Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine the Cmax for Part 1. |
| Part 1 Single dose: Concentration at 24 Hours (C24) of MK-7602 | Pre-dose of MK-7602 on Day 8 and post-dose of MK-7602 at 0.5, 1, 2, 3, 4, 8, 12, 24, 30, 36, 48, 54, 60, 72 and 96 hours and then once daily on Days 13, 15, 17, 20, and 22 | Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine the C24 for Part 1. |
| Part 1 Single dose: Time to Maximum Plasma Concentration (Tmax) of MK-7602 | Pre-dose of MK-7602 on Day 8 and post-dose of MK-7602 at 0.5, 1, 2, 3, 4, 8, 12, 24, 30, 36, 48, 54, 60, 72 and 96 hours and then once daily on Days 13, 15, 17, 20, and 22 | Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine the Tmax for Part 1. |
| Part 1 Single dose: Elimination Half-life (t1/2) of MK-7602 | Pre-dose of MK-7602 on Day 8 and post-dose of MK-7602 at 0.5, 1, 2, 3, 4, 8, 12, 24, 30, 36, 48, 54, 60, 72 and 96 hours and then once daily on Days 13, 15, 17, 20, and 22 | Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine the t1/2 for Part 1. |
| Part 2 Multiple dose: Area Under the Curve Time 0 to End of the Dosing Interval (AUC0-tau) of MK-7602 | Pre-dose of MK-7602 on Day 8 and post-first dose of MK-7602 at 0.5, 1, 2, 3, 4, 8, 12, 24, 30, 36, 48, 54, 60, 72, 78, 84 and 96 hours and then once daily on Days 13, 15, 17, 20, and 22 | Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine the AUC0-tau for Part 2. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Discontinue Study Intervention Due to an AE | Up to Day 13 | An AE is defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product and does not imply any judgment about causality. |
| Number of Participants Who Experience an Adverse Event (AE) | Up to Day 45 | An AE is defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product and does not imply any judgment about causality. |
Countries
Australia
Outcome results
None listed