Tuberculosis
Conditions
Brief summary
The goal of this clinical trial is to assess the safety, tolerability, and pharmacokinetics of single and then multiple doses of MK-7762 (TBD09) in healthy volunteers in the context of a first-in-human study. The effect of food on the rate and extent of absorption of a single oral dose of MK-7762 (TBD09) will also be evaluated.
Detailed description
This is a 2-part blinded, placebo-controlled, combined single ascending dose with a food effect cohort and multiple ascending dose trial to be conducted in one trial center in the United States. Part 1 has a single ascending dose (SAD) design with up to 5 planned dose levels. Based on the interim PK results reviewed for the dose escalation decisions, a dose will be selected for administration to a sixth cohort both in fed and fasted states to evaluate the effect of food on MK-7762 (TBD09). Safety will be assessed throughout the study; cardiac monitoring/serial ECGs and serial blood samples will be collected for the safety and PK assessment of MK7762 (TBD09). Dose escalation to the next cohort (i.e., dose level) will not take place until the Sponsor, in conjunction with the Principal Investigator, has determined that adequate safety, tolerability (and PK for the later cohorts) from the previous cohort has been demonstrated to permit proceeding to the next cohort. Interim PK analyses will be performed for the dose escalation decisions (after cohorts 1 and 2 are completed), to select the intermediate dose for the food effect cohort, and to reconsider the sampling time points as the trial progresses. All samples will be sent for analysis and the bioanalytical lab will be unblinded and only run the analysis on active treatment participants. At the escalation meetings, PK analyses from active treatment participants and blinded (pooled) safety summaries will be reviewed. All participants in Part 1 will remain at the trial site from Day -1 until their end of-trial visit (approximately 8 days for Cohorts 1-5 and 16 days for Cohort 6). At the end of Part 1, pharmacokinetic and unblinded safety data along with dose rationale for Part 2 will be sent to the Food and Drug Administration (FDA) for review and approval. The trial will not proceed to Part 2 until the FDA provides approval. Part 2 has a multiple ascending dose (MAD) design. The dose cohorts for Part 2 will be determined based on model predictions to determine the steady-state Cmax exposure, and safety from Part 1. In this MAD part, each participant will be administered MK7762 or matching placebo for 28 days with corresponding PK measurements. Three dose cohorts are planned. After each dose cohort, the Sponsor and Investigator will review the PK and safety data before proceeding to the next dose level.
Interventions
DRUGMK-7762 (TBD09)
Cohort 1: 50 mg Cohort 2: 150 mg Cohort 3: 300 mg Cohort 4: 600 mg Cohort 5: TBD Cohort 6: TBD
OTHERPlacebo
A subset of participants from each of the 6 dosing cohorts will receive placebo.
Sponsors
Gates Medical Research Institute
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
19 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
To be included in this trial, an individual must satisfy all the following criteria: 1. Is ≥ 19 to ≤ 55 years of age. 2. Is healthy as determined by the Investigator via medical history and clinical examination before enrollment in the trial. 3. Can understand and comply with the trial and site procedures, understand the risks involved in the trial, and provide written informed consent before the first trial-specific procedure. 4. Can complete all Screening period evaluations and stay in the clinical research facility for the duration of the inpatient periods of the trial. 5. Has BMI between 18 and 32 kg/m2, inclusive, and body weight not less than 50 kg at Screening. 6. Has resting vital signs at Screening within the following ranges: Systolic blood pressure (SBP) ≥100 mmHg Diastolic blood pressure (DBP) ≥50 mmHg Heart rate ≤100 beats per minute (bpm) Note: If vital signs are out of range, the Investigator may obtain two additional readings within the Screening period. 7. Has a 12-lead ECG consistent with normal cardiac conduction and function at Screening, including: HR between 45 and 100 bpm (inclusive); QTcF ≤450 ms for males and ≤470 ms for females; QRS interval \<120 ms; PR interval \<220 ms; and morphology consistent with healthy cardiac conduction. 8. Is a nonsmoker within the previous 6 months before Screening, and does not use tobacco containing, or nicotine-containing products, including, but not limited to, cigarettes, pipes, cigars, chewing tobacco, e-cigarettes, nicotine patch, or nicotine gum. 9. Has clinical chemistry, hematology, coagulation, and complete urinalysis (fasted for at least 8 hours) results at Screening within the reference range for the testing laboratory unless the out-of-range results are deemed not clinically significant by the Investigator. 10. Has negative results for hepatitis B surface antigen (HbsAg) and hepatitis C virus antibody (HCV Ab) within 3 months prior to Day -1 or at Screening. 11. Has negative test results for HIV antibody within 3 months prior to Day -1 or at Screening. 12. Has a negative urine drug screen result at Screening and on Day -1. The presence of alcohol or marijuana in the urine is not exclusionary unless the Investigator determines that the participant's marijuana use qualifies as substance abuse (see Section 5.2,
Exclusion criteria
6). 13. If individual's assigned sex at birth is female, they must be of non-childbearing potential based on either of the following: a. Is post-menopausal defined as amenorrhea for at least 12 months in absence of any exogenous hormonal treatments and follicle stimulating hormone (FSH) levels in the laboratory-defined postmenopausal range, or, b. Reports being surgically sterilized (i.e., tubal ligation, hysterectomy, bilateral oophorectomy/salpingectomy) 14. If individual is assigned male sex at birth, is not sterilized, and is sexually active with a female partner of childbearing potential, agrees to use condoms from Day -1 through 90 days after the last dose of study drug. They must also agree to not donate sperm during the trial and for 3 months (90 days) after receiving the last dose of study drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Percentage of Participants Reporting Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESIs) | Day 1 through Day 7 | An AE is any untoward medical occurrence in a clinical study participant whether or not considered related to the study intervention. A TEAE is any AE that occurs after receipt of one or more doses of study drug through the end of study for that participant. A SAE is defined as any untoward medical occurrence that, at any dose: results in death or is life-threatening or requires inpatient hospitalization or prolongation of existing hospitalization or results in persistent disability/incapacity or is a congenital anomaly/birth defect or is a medically significant / important event or reaction. AESIs are adverse events that the Sponsor monitored carefully and were subject to expedited reporting to the Sponsor. |
| Part 1: Percentage of Participants Reporting TEAEs by Severity | Day 1 through Day 7 | An AE is any untoward medical occurrence in a clinical study participant whether or not considered related to the study intervention. A TEAE is any AE that occurs after receipt of one or more doses of study drug through the end of study for that participant. The intensity for each AE reported during the study were assigned to 1 of 5 categories: Grade 1 Mild symptoms, causing no or minimal interference with usual social and functional activities with intervention not indicated; Grade 2 Moderate symptoms, causing greater than minimal interference with usual social and functional activities with intervention indicated; Grade 3 Severe symptoms, causing inability to perform usual social and functional activities with intervention or hospitalization indicated; Grade 4 Potentially life-threatening symptoms, causing inability to perform basic self-care functions with intervention indicated to prevent permanent impairment, persistent disability, or death and Grade 5: Fatal. |
| Part 1: Percentage of Participants Reporting Study Drug Related TEAEs | Day 1 through Day 7 | An AE is any untoward medical occurrence in a clinical study participant whether or not considered related to the study intervention. A TEAE is any AE that occurs after receipt of one or more doses of study drug through the end of study for that participant. |
| Part 2: FE Cohort 7: Percentage of Participants Reporting TEAEs, SAEs, and AESIs | Up to Day 7 | An AE is any untoward medical occurrence in a clinical study participant whether or not considered related to the study intervention. A TEAE is any AE that occurs after receipt of one or more doses of study drug through the end of study for that participant. A SAE is defined as any untoward medical occurrence that, at any dose: results in death or is life-threatening or requires inpatient hospitalization or prolongation of existing hospitalization or results in persistent disability/incapacity or is a congenital anomaly/birth defect or is a medically significant / important event or reaction. AESIs are adverse events that the Sponsor monitored carefully and were subject to expedited reporting to the Sponsor. |
| Part 2: FE Cohort 7: Percentage of Participants Reporting Study Drug Related TEAEs | Up to Day 7 | An AE is any untoward medical occurrence in a clinical study participant whether or not considered related to the study intervention. A TEAE is any AE that occurs after receipt of one or more doses of study drug through the end of study for that participant. |
| Part 2: FE Cohort 7: Percentage of Participants Reporting TEAEs by Severity | Up to Day 7 | An AE is any untoward medical occurrence in a clinical study participant whether or not considered related to the study intervention. A TEAE is any AE that occurs after receipt of one or more doses of study drug through the end of study for that participant. The intensity for each AE reported during the study were assigned to 1 of 5 categories: Grade 1 Mild symptoms, causing no or minimal interference with usual social and functional activities with intervention not indicated; Grade 2 Moderate symptoms, causing greater than minimal interference with usual social and functional activities with intervention indicated; Grade 3 Severe symptoms, causing inability to perform usual social and functional activities with intervention or hospitalization indicated; Grade 4 Potentially life-threatening symptoms, causing inability to perform basic self-care functions with intervention indicated to prevent permanent impairment, persistent disability, or death and Grade 5: Fatal. |
| Part 2: MAD Cohorts: Percentage of Participants Reporting TEAEs, SAEs, and AESIs | Day 1 through Day 36. | An AE is any untoward medical occurrence in a clinical study participant whether or not considered related to the study intervention. A TEAE is any AE that occurs after receipt of one or more doses of study drug through the end of study for that participant. A SAE is defined as any untoward medical occurrence that, at any dose: results in death or is life-threatening or requires inpatient hospitalization or prolongation of existing hospitalization or results in persistent disability/incapacity or is a congenital anomaly/birth defect or is a medically significant / important event or reaction. AESIs are adverse events that the Sponsor monitored carefully and were subject to expedited reporting to the Sponsor. |
| Part 2: MAD Cohorts: Percentage of Participants Reporting TEAEs by Severity | Day 1 through Day 36. | An AE is any untoward medical occurrence in a clinical study participant whether or not considered related to the study intervention. A TEAE is any AE that occurs after receipt of one or more doses of study drug through the end of study for that participant. The intensity for each AE reported during the study were assigned to 1 of 5 categories: Grade 1 Mild symptoms, causing no or minimal interference with usual social and functional activities with intervention not indicated; Grade 2 Moderate symptoms, causing greater than minimal interference with usual social and functional activities with intervention indicated; Grade 3 Severe symptoms, causing inability to perform usual social and functional activities with intervention or hospitalization indicated; Grade 4 Potentially life-threatening symptoms, causing inability to perform basic self-care functions with intervention indicated to prevent permanent impairment, persistent disability, or death and Grade 5: Fatal. |
| Part 2: MAD Cohorts: Proportion of Participants Reporting Study Drug Related TEAEs | Day 1 through Day 36 | An AE is any untoward medical occurrence in a clinical study participant whether or not considered related to the study intervention. A TEAE is any AE that occurs after receipt of one or more doses of study drug through the end of study for that participant. |
| Part 1: Number of Participants With Clinically Significant Changes in Hematology Parameters | Up to Day 7 | Blood samples were collected for the analysis of hematology parameters: complete blood count (red blood cells, hemoglobin, platelets, and white blood cells \[WBC\]); red blood cell parameters (eg, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and red cell distribution width); white blood cell differential (absolute counts), including neutrophils, lymphocytes, monocytes, eosinophils and basophils; and reticulocyte count |
| Part 1: Number of Participants With Clinically Significant Changes in Chemistry Parameters | Up to Day 7 | Blood samples were collected for the analysis of chemistry parameters: alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total and direct bilirubin, creatinine, blood urea nitrogen (BUN) or urea, creatine kinase, sodium, potassium, bicarbonate or CO2, chloride, glucose, and lipid profile (total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides. |
| Part 1: Number of Participants With Clinically Significant Changes in Serum Coagulation Parameters | Up to Day 7 | Blood samples were collected for the analysis of Serum coagulation parameters: Prothrombin Time (PT), Partial Thromboplastin Time (PTT), and international normalized ratio (INR). |
| Part 1: Number of Participants With Clinically Significant Changes in Urinalysis | Up to Day 7 | Urine samples were collected for the analysis of urinalysis parameters: Dipstick for potential of hydrogen (pH), specific gravity, glucose, protein, blood, leukocyte esterase, nitrites, ketones, bilirubin, and urobilinogen. Microscopic examination for red blood cells, white blood cells, casts, and bacteria was performed if urine dipstick is positive for protein, blood, leukocyte esterase, or nitrites. |
| Part 1: Number of Participants With Clinically Significant Changes in Vital Parameters | Up to Day 7 | Vital parameters including temperature, heart rate (HR), and blood pressure (BP) were measured in supine position. Data for number of participants with abnormal clinically significant changes for vital signs have been presented. |
| Part 1: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters | Up to Day 7 | ECG parameters included HR, RR interval, PR interval, QRS duration, QT interval, and QT interval corrected by Fridericia's formula (QTcF). |
| Part 2: FE Cohort 7: Number of Participants With Clinically Significant Changes in Hematology Parameters | Up to Day 8 | Blood samples were collected for the analysis of hematology parameters: complete blood count (red blood cells, hemoglobin, platelets, and WBC); red blood cell parameters (eg, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and red cell distribution width); white blood cell differential (absolute counts), including neutrophils, lymphocytes, monocytes, eosinophils and basophils; and reticulocyte count. |
| Part 2: MAD Cohorts: Number of Participants With Clinically Significant Changes in Hematology Parameters | Up to Day 36 | Blood samples were collected for the analysis of hematology parameters: complete blood count (red blood cells, hemoglobin, platelets, and WBC); red blood cell parameters (eg, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and red cell distribution width); white blood cell differential (absolute counts), including neutrophils, lymphocytes, monocytes, eosinophils and basophils; and reticulocyte count |
| Part 2: FE Cohort 7: Number of Participants With Clinically Significant Changes in Chemistry Parameters | Up to Day 8 | Blood samples were collected for the analysis of chemistry parameters: ALT, AST, ALP, total and direct bilirubin, creatinine, BUN or urea, creatine kinase, sodium, potassium, bicarbonate or CO2, chloride, glucose, and lipid profile (total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides). |
| Part 2: MAD Cohorts: Number of Participants With Clinically Significant Changes in Chemistry Parameters | Up to Day 36 | Participants were randomized to receive MK-7762 100 mg in a fed or fasted state. |
| Part 2: FE Cohort 7: Number of Participants With Clinically Significant Changes in Serum Coagulation Parameters | Up to Day 8 | Blood samples were collected for the analysis of Serum coagulation parameters: PT, PTT, and INR. |
| Part 2: FE Cohort 7: Number of Participants With Clinically Significant Changes in Urinalysis | Up to Day 8 | Urine samples were collected for the analysis of urinalysis parameters: Dipstick for pH, specific gravity, glucose, protein, blood, leukocyte esterase, nitrites, ketones, bilirubin, and urobilinogen. Microscopic examination for red blood cells, white blood cells, casts, and bacteria was performed if urine dipstick is positive for protein, blood, leukocyte esterase, or nitrites. |
| Part 2: MAD Cohorts: Number of Participants With Clinically Significant Changes in Serum Coagulation Parameters | Up to Day 36 | Blood samples were collected for the analysis of Serum coagulation parameters: PT, PTT, and INR. |
| Part 2: MAD Cohorts: Number of Participants With Clinically Significant Changes in Urinalysis | Up to Day 36 | Urine samples were collected for the analysis of urinalysis parameters: Dipstick for pH, specific gravity, glucose, protein, blood, leukocyte esterase, nitrites, ketones, bilirubin, and urobilinogen. Microscopic examination for red blood cells, white blood cells, casts, and bacteria was performed if urine dipstick is positive for protein, blood, leukocyte esterase, or nitrites |
| Part 2: FE Cohort 7: Number of Participants With Clinically Significant Changes in Vital Parameters | Up to Day 8 | Vital parameters including temperature, HR, and BP were measured in supine position. Data for number of participants with abnormal clinically significant changes for vital signs have been presented. |
| Part 2: MAD Cohorts: Number of Participants With Clinically Significant Changes in Vital Parameters | Up to Day 36 | Vital parameters including temperature, HR, and BP were measured in supine position. Data for number of participants with abnormal clinically significant changes for vital signs have been presented. |
| Part 2: FE Cohort 7: Number of Participants With Clinically Significant Changes in ECG Parameters | Up to Day 8 | ECG parameters included HR, RR interval, PR interval, QRS duration, QT interval, and QTcF. |
| Part 2: MAD Cohorts: Number of Participants With Clinically Significant Changes in ECG Parameters | Up to Day 36 | ECG parameters included HR, RR interval, PR interval, QRS duration, QT interval, and QTcF. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Maximum Plasma Drug Concentration (Cmax) of MK-7762 | Day 1: Pre-dose and at 1, 2, 3, 4, 5, 6, 8, and 12 hours post-dose and 24 and 36 hours post-dose (Day 2); Day 3: 48 hours post-dose; Day 4: 72 hours post-dose; Day 7: Within ±1-hour time window of time of study drug administration on Day 1 | Blood samples were collected at indicated time points for the analysis of pharmacokinetic parameters. Pharmacokinetics data was calculated using standard non-compartmental analysis methods. In FE cohort 6 for fasted and fed conditions, data has been collected for all fasted and fed participants. The data hence has been presented for all fasted and fed participants. |
| Part 1: Time to Maximum Plasma Drug Concentration (Tmax) of MK-7762 | Day 1: Pre-dose and at 1, 2, 3, 4, 5, 6, 8, and 12 hours post-dose and 24 and 36 hours post-dose (Day 2); Day 3: 48 hours post-dose; Day 4: 72 hours post-dose; Day 7: Within ±1-hour time window of time of study drug administration on Day 1 | Blood samples were collected at indicated time points for the analysis of pharmacokinetic parameters. Pharmacokinetics data was calculated using standard non-compartmental analysis methods. In FE cohort 6 for fasted and fed conditions, data has been collected for all fasted and fed participants. The data hence has been presented for all fasted and fed participants. |
| Part 1: Area Under the Concentration-time Curve (AUC) Calculated to Last Quantifiable Observed Sample (AUClast) of MK-7762 | Day 1: Pre-dose and at 1, 2, 3, 4, 5, 6, 8, and 12 hours post-dose and 24 and 36 hours post-dose (Day 2); Day 3: 48 hours post-dose; Day 4: 72 hours post-dose; Day 7: Within ±1-hour time window of time of study drug administration on Day 1 | Blood samples were collected at indicated time points for the analysis of pharmacokinetic parameters. Pharmacokinetics data was calculated using standard non-compartmental analysis methods. In FE cohort 6 for fasted and fed conditions, data has been collected for all fasted and fed participants. The data hence has been presented for all fasted and fed participants. |
| Part 1: AUC Over First 24h (AUC0-24) of MK-7762 | Up to 24 hrs post dose | Blood samples were collected at indicated time points for the analysis of pharmacokinetic parameters. Pharmacokinetics data was calculated using standard non-compartmental analysis methods. In FE cohort 6 for fasted and fed conditions, data has been collected for all fasted and fed participants. The data hence has been presented for all fasted and fed participants. |
| Part 1: AUC Extrapolated to Infinity (AUC0-inf) of MK-7762 | Day 1: Pre-dose and at 1, 2, 3, 4, 5, 6, 8, and 12 hours post-dose and 24 and 36 hours post-dose (Day 2); Day 3: 48 hours post-dose; Day 4: 72 hours post-dose; Day 7: Within ±1-hour time window of time of study drug administration on Day 1 | Blood samples were collected at indicated time points for the analysis of pharmacokinetic parameters. Pharmacokinetics data was calculated using standard non-compartmental analysis methods. In FE cohort 6 for fasted and fed conditions, data has been collected for all fasted and fed participants. The data hence has been presented for all fasted and fed participants. |
| Part 1: Terminal Elimination Half-life (t½) of MK-7762 | Day 1: Pre-dose and at 1, 2, 3, 4, 5, 6, 8, and 12 hours post-dose and 24 and 36 hours post-dose (Day 2); Day 3: 48 hours post-dose; Day 4: 72 hours post-dose; Day 7: Within ±1-hour time window of time of study drug administration on Day 1 | Blood samples were collected at indicated time points for the analysis of pharmacokinetic parameters. Pharmacokinetics data was calculated using standard non-compartmental analysis methods. In FE cohort 6 for fasted and fed conditions, data has been collected for all fasted and fed participants. The data hence has been presented for all fasted and fed participants. |
| Part 1: Oral Clearance (CL/F) of MK-7762 | Day 1: Pre-dose and at 1, 2, 3, 4, 5, 6, 8, and 12 hours post-dose and 24 and 36 hours post-dose (Day 2); Day 3: 48 hours post-dose; Day 4: 72 hours post-dose; Day 7: Within ±1-hour time window of time of study drug administration on Day 1 | Blood samples were collected at indicated time points for the analysis of pharmacokinetic parameters. Pharmacokinetics data was calculated using standard non-compartmental analysis methods. In FE cohort 6 for fasted and fed conditions, data has been collected for all fasted and fed participants. The data hence has been presented for all fasted and fed participants. |
| Part 1: Oral Volume of Distribution (Vd/F) of MK-7762 | Day 1: Pre-dose and at 1, 2, 3, 4, 5, 6, 8, and 12 hours post-dose and 24 and 36 hours post-dose (Day 2); Day 3: 48 hours post-dose; Day 4: 72 hours post-dose; Day 7: Within ±1-hour time window of time of study drug administration on Day 1 | Blood samples were collected at indicated time points for the analysis of pharmacokinetic parameters. Pharmacokinetics data was calculated using standard non-compartmental analysis methods. In FE cohort 6 for fasted and fed conditions, data has been collected for all fasted and fed participants. The data hence has been presented for all fasted and fed participants. |
| Part 2: FE Cohort 7: Cmax of MK-7762 | Day 1: pre-dose and at 1, 2, 4, 6, 8, and 12 hours post dose and 24- and 36-hours post-dose (Day 2); Day 3: 48 hours; Day 4: 72 hours; Day 5: 96 hours; Day 6: 120 hours; Day 7: 144 hours; Day 8: 168 hours post dose | Blood samples were collected at indicated time points for the analysis of pharmacokinetic parameters. Pharmacokinetics data was calculated using standard non-compartmental analysis methods. |
| Part 2: FE Cohort 7: Tmax of MK-7762 | Day 1: pre-dose and at 1, 2, 4, 6, 8, and 12 hours post dose and 24- and 36-hours post-dose (Day 2); Day 3: 48 hours; Day 4: 72 hours; Day 5: 96 hours; Day 6: 120 hours; Day 7: 144 hours; Day 8: 168 hours post dose | Blood samples were collected at indicated time points for the analysis of pharmacokinetic parameters. Pharmacokinetics data was calculated using standard non-compartmental analysis methods. |
| Part 2: FE Cohort 7: AUClast of MK-7762 | Day 1: pre-dose and at 1, 2, 4, 6, 8, and 12 hours post dose and 24- and 36-hours post-dose (Day 2); Day 3: 48 hours; Day 4: 72 hours; Day 5: 96 hours; Day 6: 120 hours; Day 7: 144 hours; Day 8: 168 hours post dose | Blood samples were collected at indicated time points for the analysis of pharmacokinetic parameters. Pharmacokinetics data was calculated using standard non-compartmental analysis methods. |
| Part 2: FE Cohort 7: AUC0-inf of MK-7762 | Day 1: pre-dose and at 1, 2, 4, 6, 8, and 12 hours post dose and 24- and 36-hours post-dose (Day 2); Day 3: 48 hours; Day 4: 72 hours; Day 5: 96 hours; Day 6: 120 hours; Day 7: 144 hours; Day 8: 168 hours post dose | Blood samples were collected at indicated time points for the analysis of pharmacokinetic parameters. Pharmacokinetics data was calculated using standard non-compartmental analysis methods. |
| Part 2: FE Cohort 7: AUC0-24 of MK-7762 | Up to 24 hours post dose | Blood samples were collected at indicated time points for the analysis of pharmacokinetic parameters. Pharmacokinetics data was calculated using standard non-compartmental analysis methods. |
| Part 2: FE Cohort 7: t½ of MK-7762 | Day 1: pre-dose and at 1, 2, 4, 6, 8, and 12 hours post dose and 24- and 36-hours post-dose (Day 2); Day 3: 48 hours; Day 4: 72 hours; Day 5: 96 hours; Day 6: 120 hours; Day 7: 144 hours; Day 8: 168 hours post dose | Blood samples were collected at indicated time points for the analysis of pharmacokinetic parameters. Pharmacokinetics data was calculated using standard non-compartmental analysis methods. |
| Part 2: FE Cohort 7: CL/F of MK-7762 | Day 1: pre-dose and at 1, 2, 4, 6, 8, and 12 hours post dose and 24- and 36-hours post-dose (Day 2); Day 3: 48 hours; Day 4: 72 hours; Day 5: 96 hours; Day 6: 120 hours; Day 7: 144 hours; Day 8: 168 hours post dose | Blood samples were collected at indicated time points for the analysis of pharmacokinetic parameters. Pharmacokinetics data was calculated using standard non-compartmental analysis methods. |
| Part 2: FE Cohort 7: Vd/F of MK-7762 | Day 1: pre-dose and at 1, 2, 4, 6, 8, and 12 hours post dose and 24- and 36-hours post-dose (Day 2); Day 3: 48 hours; Day 4: 72 hours; Day 5: 96 hours; Day 6: 120 hours; Day 7: 144 hours; Day 8: 168 hours post dose | Blood samples were collected at indicated time points for the analysis of pharmacokinetic parameters. Pharmacokinetics data was calculated using standard non-compartmental analysis methods. |
| Part 2: MAD Cohorts: CL/F of MK-7762 | Day 28: pre-dose, and at 1, 2, 4, 6, 8, and 12 hours post dose | Blood samples were collected at indicated time points for the analysis of pharmacokinetic parameters. Pharmacokinetics data was calculated using standard non-compartmental analysis methods. |
| Part 2: MAD Cohorts: Vz/F of MK-7762 | Day 28: pre-dose, and at 1, 2, 4, 6, 8, and 12 hours post dose | Blood samples were collected at indicated time points for the analysis of pharmacokinetic parameters. Pharmacokinetics data was calculated using standard non-compartmental analysis methods. |
| Part 2: MAD Cohorts: Accumulation Ratio (RA AUC0-24) of MK-7762 | Day 1: predose and at 1, 2, 4, 6, 8, and 12 hours post dose; Day 28: pre-dose, and at 1, 2, 4, 6, 8, and 12 hours post dose | Blood samples were collected at indicated time points for the analysis of pharmacokinetic parameters. Pharmacokinetics data was calculated using standard non-compartmental analysis methods. Accumulation ratio based on AUC 0-24 was calculated as AUC tau (Day 28) /AUC 0-24 (Day 1). |
| Part 2: MAD Cohorts: Cmax of MK-7762 | Day 1: pre-dose and at 1, 2, 4, 6, 8, and 12 hours post dose; Day 28: pre-dose, and at 1, 2, 4, 6, 8, and 12 hours postdose | Blood samples were collected at indicated time points for the analysis of pharmacokinetic parameters. Pharmacokinetics data was calculated using standard non-compartmental analysis methods. |
| Part 2: MAD Cohorts: Tmax of MK-7762 | Day 1: pre-dose and at 1, 2, 4, 6, 8, and 12 hours post dose; Day 28: pre-dose, and at 1, 2, 4, 6, 8, and 12 hours postdose | Blood samples were collected at indicated time points for the analysis of pharmacokinetic parameters. Pharmacokinetics data was calculated using standard non-compartmental analysis methods. |
| Part 2: MAD Cohorts: AUC0-24 of MK-7762 | Up to 24 hours post dose | Blood samples were collected at indicated time points for the analysis of pharmacokinetic parameters. Pharmacokinetics data was calculated using standard non-compartmental analysis methods. |
| Part 2: MAD Cohorts: AUClast of MK-7762 | Day 28: pre-dose, and at 1, 2, 4, 6, 8, and 12 hours postdose | Blood samples were collected at indicated time points for the analysis of pharmacokinetic parameters. Pharmacokinetics data was calculated using standard non-compartmental analysis methods. |
| Part 2: MAD Cohorts: AUC0-inf of MK-7762 | Day 28: pre-dose, and at 1, 2, 4, 6, 8, and 12 hours post dose | Blood samples were collected at indicated time points for the analysis of pharmacokinetic parameters. Pharmacokinetics data was calculated using standard non-compartmental analysis methods. |
| Part 2: MAD Cohorts: t1/2 of MK-7762 | Day 28: pre-dose, and at 1, 2, 4, 6, 8, and 12 hours post dose | Blood samples were collected at indicated time points for the analysis of pharmacokinetic parameters. Pharmacokinetics data was calculated using standard non-compartmental analysis methods. |
Countries
United States
Contacts
STUDY_DIRECTORGates MRI
Gates MRI
Participant flow
Recruitment details
This was a first-in-human trial of MK-7762, administered orally to healthy adults. It was a randomized, placebo-controlled, two-part trial. Part 1 consisted of double-blind single ascending dose (SAD) Cohorts 1 to 5, and food effect (FE) Cohort 6 (open-label). Part 2 consisted of a FE cohort 7 (open-label) and three sequential double-blind multiple ascending dose (MAD) cohorts (Cohorts 8 to 10).
Pre-assignment details
A total of 119 participants (including 2 replacement participants in Part 2) were dosed (48 in Part 1 and 71 in Part 2), and a total of 97 participants were exposed to MK-7762 (38 from Part 1 and 59 from Part 2).
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 37.9 Years STANDARD_DEVIATION 8.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 41 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 70 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 10 | 0 / 8 | 0 / 8 | 0 / 10 | 0 / 10 | 0 / 9 | 0 / 16 | 0 / 16 | 0 / 16 | 0 / 12 |
| other Total, other adverse events | 0 / 6 | 0 / 6 | 1 / 6 | 1 / 6 | 1 / 6 | 2 / 10 | 0 / 8 | 1 / 8 | 5 / 10 | 4 / 10 | 5 / 9 | 12 / 16 | 10 / 16 | 14 / 16 | 8 / 12 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 10 | 0 / 8 | 0 / 8 | 0 / 10 | 0 / 10 | 0 / 9 | 0 / 16 | 0 / 16 | 0 / 16 | 0 / 12 |
Outcome results
None listed