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Study to Determine the Single and Repeat Dose Pharmacokinetics, Food Effect, Proton Pump Inhibitor (PPI) Drug Interaction, Safety and Tolerability of Oral Prototype Formulations of BOS172767 in Healthy Subjects

17 novembre 2020 mis à jour par: Boston Pharmaceuticals

A Phase 1 Study to Determine the Single and Repeat Dose Pharmacokinetics, Food Effect, PPI Drug Interaction, Safety and Tolerability of Oral Prototype Formulations of BOS172767 in Healthy Subjects

Part 1 of the study will be conducted to provide additional information on the safety and tolerability of single doses of BOS172767 in healthy participants, to evaluate the pharmacokinetic (PK) profiles (including relative bioavailability) of BOS172767 following oral administration of 3 prototype formulations in healthy participants compared to an immediate release capsule formulation (reference), and also to determine the relative bioavailability of a selected BOS172767 prototype formulation in the fed and fasted states.

Part 2 of the study will be conducted to provide additional information on the safety and tolerability of escalating single doses of the selected formulation of BOS172767 in healthy participants, to evaluate the PK profile following increased single doses of the selected formulation of BOS172767 following administration in healthy participants, and also to evaluate the dose linearity of the selected prototype.

Part 3 of the study will be conducted to provide additional information on the safety, tolerability, and PK of the selected formulation of BOS172767 following multiple ascending doses (MADs) over 14 days of dosing in healthy participants.

Aperçu de l'étude

Description détaillée

Part 1 is comprised of a single-dose, part-randomized, open-label, 6-way crossover in 12 healthy participants. Participants will be dosed on 6 separate occasions (in 6 treatment periods), and will receive a single prototype of BOS172767 in each treatment period.

Part 2 is comprised of a single ascending dose, fixed-sequence, open-label, 3-way crossover with an optional fourth dosing period in 10 healthy participants. Participants will be dosed on 4 separate occasions (in 4 treatment periods), and will receive a single prototype of BOS172767 in each treatment period.

Part 3 is a double-blind (sponsor-open), placebo-controlled, randomized MAD part in 36 healthy participants (12 per study cohort). Participants will be dosed on 3 separate occasions (in 3 treatment periods), and will receive a single prototype of BOS172767 in each treatment period.

Parts 2 and 3 are contingent upon successful completion of Part 1.

Type d'étude

Interventionnel

Inscription (Réel)

28

Phase

  • La phase 1

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

      • Nottingham, Royaume-Uni
        • Quotient Sciences

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 50 ans (Adulte)

Accepte les volontaires sains

Oui

Sexes éligibles pour l'étude

Tout

La description

Inclusion Criteria:

  • Healthy males or healthy females of non-child bearing potential
  • Age 18 to 50 years of age at time of signing informed consent
  • Body mass index of 18.0 to 32.0 kilograms per meters squared (kg/m^2) at Screening, or, if outside the range, considered not clinically significant by the investigator
  • Must be willing and able to communicate and participate in the whole study
  • Must have a negative Quantiferon tuberculosis test at Screening
  • Must provide written informed consent
  • Must agree to use an adequate method of contraception

Exclusion Criteria:

  • Participants who have received any investigational medicinal product (IMP) in a clinical research study within the previous 3 months prior to dosing
  • Participants who are study site employees, or immediate family members of a study site or sponsor employee
  • Participants who have previously been enrolled (dosed) in this study
  • History of any drug or alcohol abuse in the past 2 years prior to Screening
  • Regular alcohol consumption in males >21 units per week and females >14 units per week (1 unit = ½ pint beer, 25 milliliters [mL] of 40% spirit or a 125 mL glass of wine)
  • Current smokers and those who have smoked within the last 12 months prior to Screening. A breath carbon monoxide reading of greater than 20 parts per million at Screening or admission
  • Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months prior to Screening
  • Females of childbearing potential
  • Participants who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator at Screening
  • Clinically significant abnormal biochemistry, haematology or urinalysis as judged by the investigator
  • Confirmed positive drugs of abuse test result
  • Positive hepatitis B surface antigen, hepatitis C virus antibody or human immunodeficiency virus results
  • Evidence of renal impairment at Screening, as indicated by an estimated creatinine clearance of <70 mL/minute using the Cockcroft-Gault equation
  • History of clinically significant cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease (including gall stones and/or cholecystectomy), neurological or psychiatric disorder, as judged by the investigator
  • Serious adverse reaction or serious hypersensitivity to any drug or the IMP formulation excipients
  • Adverse reaction to rabeprazole, its excipients or any proton pump inhibitors (Part 2 only)
  • Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever is allowed unless it is active.
  • Donation or loss of greater than 400 mL of blood within the previous 3 months
  • Participants who are taking, or have taken, any prescribed or over-the-counter drug (other than 4 grams per day paracetamol or hormone replacement therapy) or herbal remedies in the 14 days before IMP administration. Exceptions may apply on a case by case basis, if considered not to interfere with the objectives of the study, as agreed by the Principal Investigator and sponsor's medical monitor.
  • Participants who have any ongoing fungal infections (stable toe nail onychomycosis is allowed)
  • Failure to satisfy the investigator of fitness to participate for any other reason

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Science basique
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation croisée
  • Masquage: Tripler

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: Part 1: Regimen A
Participants will be treated with a BOS172767 200 milligram (mg) spray dried dispersion tablet (2 × 100 mg tablets) in the fasted state on Day 1.
Oral tablets
Expérimental: Part 1: Regimen B
Participants will be treated with a BOS172767 200 mg lipid capsule (2 × 100 mg capsules) in the fasted state on Day 1.
Oral capsules
Expérimental: Part 1: Regimen C
Participants will be treated with a BOS172767 200 mg micronized capsule (2 × 100 mg capsules) in the fasted state on Day 1.
Oral capsules
Expérimental: Part 1: Regimen D
Participants will be treated with a BOS172767 200 mg immediate release reference capsule formulation (2 × 100 mg capsules) in the fasted state on Day 1.
Oral capsules
Expérimental: Part 1: Regimen E
Participants will be treated with a selected dose of a prototype formulation of BOS172767 in the fasted state on Day 1.
Oral tablets
Oral capsules
Oral capsules
Oral capsules
Expérimental: Part 1: Regimen F
Participants will be treated with a selected dose of a prototype formulation of BOS172767 in the fed state on Day 1.
Oral tablets
Oral capsules
Oral capsules
Oral capsules
Expérimental: Part 2: Regimen G
Participants will be treated with 400 mg of the selected BOS172767 prototype in the fasted state on Day 1.
Oral tablets
Oral capsules
Oral capsules
Oral capsules
Expérimental: Part 2: Regimen H
Participants will be treated with 600 mg of the selected BOS172767 prototype in the fasted state on Day 1.
Oral tablets
Oral capsules
Oral capsules
Oral capsules
Expérimental: Part 2: Regimen I
Participants will be treated with 800 mg of the selected BOS172767 prototype in the fasted state on Day 1.
Oral tablets
Oral capsules
Oral capsules
Oral capsules
Expérimental: Part 2: Regimen J
Participants will be treated with rabeprazole on Days -3 to -1, and a selected dose of the BOS172767 prototype in the fasted state on Day 1.
Oral tablets
Oral capsules
Oral capsules
Oral capsules
Comprimés oraux
Expérimental: Part 3: Regimen K
Participants will be treated with 400 mg of a BOS172767 prototype or matching placebo once daily (QD) or twice daily (BID) for 14 days (Days 1 to 14).
Oral tablets
Oral capsules
Oral capsules
Oral capsules
Oral capsules
Oral tablets
Expérimental: Part 3: Regimen L
Participants will be treated with 600 mg of a BOS172767 prototype or matching placebo QD or BID for 14 days (Days 1 to 14).
Oral tablets
Oral capsules
Oral capsules
Oral capsules
Oral capsules
Oral tablets
Expérimental: Part 3: Regimen M
Participants will be treated with 800 mg of a BOS172767 prototype or matching placebo QD or BID for 14 days (Days 1 to 14).
Oral tablets
Oral capsules
Oral capsules
Oral capsules
Oral capsules
Oral tablets

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Délai
Parts 1, 2, and 3: Number of participants with any treatment-emergent serious adverse event (TESAE)
Délai: up to 33 weeks
up to 33 weeks
Parts 1, 2, and 3: Number of participants with any treatment-emergent non-serious adverse event (TEAE)
Délai: up to 33 weeks
up to 33 weeks
Parts 1, 2, and 3: Number of participants with abnormal, clinically significant physical examination findings
Délai: up to 33 weeks
up to 33 weeks
Parts 1, 2, and 3: Number of participants with abnormal, clinically significant safety laboratory test findings
Délai: up to 33 weeks
up to 33 weeks
Parts 1, 2, and 3: Number of participants with abnormal, clinically significant vital sign values
Délai: up to 33 weeks
up to 33 weeks
Parts 1, 2, and 3: Number of participants with abnormal, clinically significant electrocardiogram findings
Délai: up to 33 weeks
up to 33 weeks
Parts 1 and 2: Plasma concentration of BOS172722
Délai: predose; 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16 hours postdose (Day 1); 24 and 36 hours postdose (Day 2); 48 hours postdose (Day 3)
predose; 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16 hours postdose (Day 1); 24 and 36 hours postdose (Day 2); 48 hours postdose (Day 3)
Part 2 (Regimen I): Plasma concentration of BOS172722
Délai: admission to pre-dose (admission to dosing), 0 to 6 (Day 1), 6 to 12 (Day 1), 12 to 24 (Day 1), and 24 to 48 (Days 2 to 3) hours postdose
admission to pre-dose (admission to dosing), 0 to 6 (Day 1), 6 to 12 (Day 1), 12 to 24 (Day 1), and 24 to 48 (Days 2 to 3) hours postdose
Part 3: Plasma concentration of BOS172722
Délai: Days 1 and 7: pre-dose; 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours postdose. Days 4, 6, 9, 11, and 12: pre-dose. Day 14: pre-dose; 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, and 120 hours post-final dose
Days 1 and 7: pre-dose; 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours postdose. Days 4, 6, 9, 11, and 12: pre-dose. Day 14: pre-dose; 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, and 120 hours post-final dose
Part 3 (Regimen M): Plasma concentration of BOS172722
Délai: admission to pre-dose on Day 1; 0 to 6, 6 to 12, and 12 to 24 hours postdose on Days 1, 7, and 14
admission to pre-dose on Day 1; 0 to 6, 6 to 12, and 12 to 24 hours postdose on Days 1, 7, and 14

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

21 mars 2018

Achèvement primaire (Réel)

9 octobre 2018

Achèvement de l'étude (Réel)

10 octobre 2018

Dates d'inscription aux études

Première soumission

7 mars 2018

Première soumission répondant aux critères de contrôle qualité

7 mars 2018

Première publication (Réel)

13 mars 2018

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

18 novembre 2020

Dernière mise à jour soumise répondant aux critères de contrôle qualité

17 novembre 2020

Dernière vérification

1 novembre 2020

Plus d'information

Termes liés à cette étude

Autres numéros d'identification d'étude

  • BOS172767-01
  • 2017-004002-18 (Numéro EudraCT)
  • QCL118174 (Autre identifiant: Quotient Study Number)

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Oui

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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