Terminé

A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) Trial in Healthy Adults to Evaluate the Safety, Tolerability, and PK of MK-7762

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Ce qui est testé

MK-7762 (TBD09)

+ Placebo
Médicament
Autre
Qui peut participer

Infections à Actinomycétales
+4

+ Infections bactériennes
+ Infections bactériennes et mycoses
De 19 à 55 ans
Voir tous les critères d'éligibilité
Comment se déroule l'étude

Étude thérapeutique

Groupe Placebo
Phase 1
Interventionnel
Date de début : février 2023
Voir le détail du protocole

Résumé

Sponsor principalBill & Melinda Gates Medical Research Institute
Dernière mise à jour : 13 décembre 2025
Issu d'une base de données validée par les autorités. Revendiquer cette étude
Date de début de l'étude : 23 février 2023Date à laquelle le premier participant a commencé l'étude.

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.

Titre officielA Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) Trial in Healthy Adults to Evaluate the Safety, Tolerability, and PK of MK-7762 
NCT05824091
Sponsor principalBill & Melinda Gates Medical Research Institute
Dernière mise à jour : 13 décembre 2025
Issu d'une base de données validée par les autorités. Revendiquer cette étude

Protocole

Cette section fournit des détails sur le plan de l'étude, y compris la manière dont l'étude est conçue et ce qu'elle évalue.
Détails du design
119 participants à inclureNombre total de participants que l'essai clinique vise à recruter.
Traitement
Cette étude teste un ou plusieurs traitements pour évaluer leur efficacité contre une maladie ou un problème de santé spécifique. L'objectif est de voir si un nouveau médicament ou une thérapie fonctionne mieux, ou provoque moins d'effets secondaires que les options existantes.

Comment les participants sont répartis entre les groupes de l'étude
Dans cette étude clinique, les participants sont répartis de manière aléatoire, comme lors d'un tirage au sort. Cela garantit l'équité et réduit les biais, rendant les résultats plus fiables. En attribuant les participants au hasard, les chercheurs peuvent comparer les traitements sans influence extérieure.

Autres méthodes de répartition
Répartition non aléatoire
: basée sur des critères spécifiques comme l'état de santé ou la décision du médecin.

Aucune (un seul groupe de participants)
: tous les participants reçoivent le même traitement, aucune répartition n'est nécessaire.

Comment les traitements sont administrés aux participants
Les participants reçoivent les traitements les uns après les autres, selon une séquence prédéfinie. Le traitement suivant peut dépendre de la façon dont le participant réagit au précédent.

Autres façons d'administrer les traitements
Groupe unique
: tous les participants reçoivent le même traitement.

Affectation parallèle
: les participants sont répartis en groupes recevant chacun un traitement différent.

Affectation croisée
: les participants passent d'un traitement à un autre au cours de l'étude.

Plan factoriel
: les participants reçoivent des combinaisons de traitements pour évaluer leurs interactions.

Autre type d'attribution
: L'attribution des traitements ne suit pas de schéma standard ni de protocole prédéfini.

Comment l'efficacité du traitement est contrôlée
Un placebo est utilisé pour comparer les effets du traitement expérimental à ceux d’une substance inactive, ce qui permet d’évaluer son efficacité réelle.

Autres options possibles
Non contrôlée par placebo
: aucun placebo n'est utilisé. Tous les participants reçoivent un traitement actif, souvent le traitement standard, pour permettre une comparaison directe.

Comment la nature du traitement est tenue confidentielle
Les participants, les chercheurs, les évaluateurs des résultats et les professionnels de santé ne savent pas quel traitement est administré. C'est la méthode la plus complète pour éviter les biais et garantir la neutralité de l'étude.

Autres méthodes de masquage
En ouvert
: tout le monde connaît le traitement administré.

Simple aveugle
: les participants ignorent le traitement reçu, mais les chercheurs le connaissent.

Double aveugle
: ni les participants ni les chercheurs ne savent quel traitement est administré.

Triple aveugle
: Les participants, les chercheurs et les personnes qui analysent les résultats ne savent pas quel traitement est administré.

Éligibilité

Les chercheurs recherchent des patients correspondant à une certaine description appelée critères d'éligibilité : état de santé général ou traitements antérieurs du patient.
Conditions
Critères
Tout sexeLe sexe biologique des participants éligibles à s'inscrire.
De 19 à 55 ansTranche d'âge des participants éligibles à participer.
Volontaires sains autorisésIndique si les individus en bonne santé et ne présentant pas la condition étudiée peuvent participer.
Conditions
Pathologie
Infections à Actinomycétales
Infections bactériennes
Infections bactériennes et mycoses
Infections
Infections à Mycobactéries
Tuberculose
Infections bactériennes à Gram-positif
Critères

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. Exclusion Criteria: If an individual meets any of the following criteria, they are ineligible for this trial: 1. Has current or past history of a clinically significant cardiovascular, cerebrovascular, respiratory, gastrointestinal, hematologic, renal, hepatic, immunologic, metabolic, urologic, neurologic, dermatologic, psychiatric, or other major disease, as determined by the Investigator. 2. Has history of or Screening findings of abnormalities of vision, including corrected visual acuity worse than 20/25 in either eye based on Screening assessment using Snellen chart and Rosenbaum pocket chart, or color vision impairment based on Screening assessment using Ishihara plates. Candidates with ametropia corrected to 20/25 or better do not have to be excluded. 3. Has history of or Screening findings of peripheral neuropathy, such as numbness or abnormal reflexes. 4. Has history of or current clinically relevant cardiovascular disorder, such as heart failure, coronary artery disease, uncontrolled hypertension, arrhythmia, tachyarrhythmia, prolonged QT syndrome, or presence of symptom(s) strongly suggestive of such a problem, such as exertional chest pressure/pain or unexplained syncope. 5. Had an active malignancy within 5 years from Screening, except basal cell or squamous cell skin cancers. Any history of breast cancer or melanoma will be exclusionary. 6. Has history of any drug abuse within 1 year prior to Screening or has used any hard drugs (such as cocaine, phencyclidine \[PCP\], natural and synthetic opiates, and amphetamine derivatives) within 1 year prior to Screening. Individuals that have taken an opioid or amphetamine medication within the previous year prior to Screening that was prescribed by a healthcare provider will not be excluded unless they are currently taking the medication at the time of Screening. 7. Has history of regular alcohol consumption exceeding 14 drinks/week (1 drink = 5 ounces \[150 mL)\] of wine or 12 ounces \[360 mL\] of beer or 1.5 ounces \[45 mL\] of hard liquor) within 6 months of Screening or alcohol abuse within 1 year prior to Screening. 8. Had any surgical or medical condition or history that, in the opinion of the Investigator, may potentially alter the absorption, metabolism, or excretion of study treatment, such as, but not limited to, gastric bypass or banding surgery or gastric or duodenal ulcers. 9. Is taking any of the following prohibited medications or vaccinations: a. Any prescription or over-the-counter medication, vitamin or dietary supplement, or herbal product within 14 days prior to Day -1. b. Received any vaccination within 14 days prior to Day -1, including COVID-19 vaccination. 10. Has a contraindication to study drugs or its excipients and/or history of a clinically significant allergic or anaphylactic reaction to a medication. 11. Has participated in other trials involving administration of an investigational drug or device within 30 days or 5 half-lives, whichever is longer, before Screening for the current trial and during participation in the current trial. 12. Has a positive PCR or antigen test result for COVID-19/SARS-CoV-2 at check-in to the Clinical Trials Unit. 13. Has a condition that the Investigator believes would interfere with the participant's ability to provide written informed consent, comply with trial instructions, or which might confound the interpretation of the trial results or put the participant at undue risk. 14. Has donated blood within 2 months before entering the trial or planning to donate blood during the trial or within 12 weeks after the final visit.


Plan de l'étude

Découvrez tous les traitements administrés dans cette étude, leur description détaillée et ce qu'ils impliquent.
Groupes de traitement
Objectifs de l'étude
2 groupes d'intervention 

sont désignés dans cette étude

50% de chances 

d'être dans le groupe placebo en aveugle

Groupes de traitement
Groupe I
Expérimental
In Part 1 of the trial (SAD/FE), up to five sequential cohorts will be enrolled to evaluate up to five escalating single doses of MK-7762; 8 participants in each cohort will be randomized (3:1) to receive MK-7762 or placebo. A sixth cohort will evaluate the effect of food on PK of single doses of MK-7762 utilizing an open-label, two-period design in 8 participants.

Cohort 1: 50 mg Cohort 2: 150 mg Cohort 3: 300 mg Cohort 4: 600 mg Cohort 5: TBD Cohort 6: TBD
Groupe II
Placebo
Participants will receive placebos matched to MK-7762 (TBD09).

A subset of participants from each of the 6 dosing cohorts will receive placebo.
Objectifs de l'étude
Objectifs principaux

Assessed by the proportion of treated participants reporting treatment-emergent adverse events (TEAEs), serious AEs (SAEs), and AEs of special interest (AESIs), assessed overall, by severity, by relationship to study drug, and by system organ class and preferred term.

Assessed by the proportion of treated participants reporting treatment-emergent adverse events (TEAEs), serious AEs (SAEs), and AEs of special interest (AESIs), assessed overall, by severity, by relationship to study drug, and by system organ class and preferred term.

Assessed by the proportion of treated participants reporting treatment-emergent adverse events (TEAEs), serious AEs (SAEs), and AEs of special interest (AESIs), assessed overall, by severity, by relationship to study drug, and by system organ class and preferred term.

In treated participants, summaries (descriptive statistics and frequencies) of safety laboratory measures (by visit, worst grade, grade shift from baseline) according to the same windows defined above for AEs.

In treated participants, summaries (descriptive statistics and frequencies) of safety laboratory measures (by visit, worst grade, grade shift from baseline) according to the same windows defined above for AEs.

In treated participants, 12-lead ECG parameters including ECG QT interval with correction factors, heart rate, RR interval, PR interval (by visit, change from baseline) according to the same windows defined above for AEs.

In treated participants, 12-lead ECG parameters including ECG QT interval with correction factors, heart rate, RR interval, PR interval (by visit, change from baseline) according to the same windows defined above for AEs.

In treated participants, vital signs (by visit, change from baseline) according to the same windows defined above for AEs.

In treated participants, vital signs (by visit, change from baseline) according to the same windows defined above for AEs.
Objectifs secondaires

Maximum plasma drug concentration (Cmax)

Time to maximum plasma drug concentration (Tmax)

Area under the concentration-time curve (AUC) calculated over the first 24h (AUC(0-24)

AUC calculated over a dosing interval (AUCTau)

AUC calculated to last quantifiable observed sample (AUC(0-last))

AUC calculated to last quantifiable observed sample (AUC(0-last))

AUC extrapolated to infinity (AUC(0-inf))

AUC extrapolated to infinity (AUC(0-inf))

Terminal elimination half-life (t½)

Terminal elimination half-life (t½)

Oral clearance (CL/F)

Oral clearance (CL/F)

Oral volume of distribution (Vd/F)

Oral volume of distribution (Vd/F)

Accumulation ratio (AUCTau / AUC(0-24))

AUC(0-inf) fasted state / AUC(0-inf) fed state

Cmax fasted state / Cmax fed state

Centres d'étude

Ce sont les hôpitaux, cliniques ou centres de recherche où l'essai est conduit. Vous pouvez trouver le site le plus proche de vous ainsi que son statut.
Cette étude comporte 1 site
Suspendu
Investigational SiteLincoln, United StatesVoir le site

Terminé1 Centres d'Étude
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