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Study to Determine the Relative Bioavailability, Single and Repeat Dose Pharmacokinetics, Safety and Tolerability of BOS172767 Enantiomers in Healthy Subjects

17 novembre 2020 aggiornato da: Boston Pharmaceuticals

A Phase 1 Study to Determine the Relative Bioavailability of BOS172767 Enantiomer E1 and E2 and the Single and Repeat Dose Pharmacokinetics, Safety and Tolerability of BOS172767 Selected Enantiomer in Healthy Subjects

Part 1 of the study evaluates the safety and tolerability as well as pharmacokinetic properties of a single oral dose of BOS172767 enantiomer E1 and BOS172767 enantiomer E2 following administration to healthy participants. Part 2 of the study was to be conducted to assess the safety and tolerability as well as pharmacokinetic properties of one selected enantiomer (BOS172767-Ex) following multiple ascending doses over 14 days of dosing in healthy participants.

Panoramica dello studio

Stato

Completato

Condizioni

Descrizione dettagliata

The study design of Part 1 was a double-blind, placebo-controlled, randomized, single-dose, two-way crossover, followed by two sequential ascending dose periods in 12 healthy participants.

Part 2 was designed to be a double-blind, placebo-controlled, randomized multiple ascending dose (MAD) study in 36 healthy participants (12 per study cohort).

Part 2 was to progress following completion of Part 1, but was not conducted.

Tipo di studio

Interventistico

Iscrizione (Effettivo)

12

Fase

  • Fase 1

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

      • Nottingham, Regno Unito
        • Quotient Sciences

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

Da 18 anni a 50 anni (Adulto)

Accetta volontari sani

Sessi ammissibili allo studio

Tutto

Descrizione

Inclusion Criteria:

  • Healthy males or healthy females of non-childbearing potential
  • Age 18 to 50 years at the time of signing informed consent
  • Body mass index (BMI) of 18.0 to 32.0 kilograms per meters squared (kg/m^2) as measured at screening
  • Must have been willing and able to communicate and participate in the whole study
  • Must have provided written informed consent
  • Must have agreed to adhere to the contraception requirements for this study

Exclusion Criteria:

  • Participants who received any investigational medicinal product (IMP) in a clinical research study within the 90 days prior to Day 1
  • Participants who were study site employees, or immediate family members of a study site or sponsor employee
  • Participants who had previously been enrolled and dosed in this study. Participants who had taken part in Part 1 were not permitted to take part in Part 2. Participants who had taken part in study QCL118174/BOS172767-01 (NCT03464058) were allowed to participate in this study.
  • History of any drug or alcohol abuse in the past 2 years
  • Regular alcohol consumption in males >21 units per week and females >14 units per week (1 unit = 1/2 pint beer, or a 25 milliliter [mL] shot of 40% spirit, 1.5 to 2 Units = 125 mL glass of wine, depending on type)
  • A confirmed positive alcohol breath test at screening or admission
  • Current smokers and those who had smoked within the last 6 months. A confirmed breath carbon monoxide reading of greater than 20 parts per million (ppm) at screening or admission.
  • Current users of e-cigarettes and nicotine replacement products and those who had used these products within the last 6 months
  • Females of childbearing potential including those who were pregnant or lactating (all female participants must have had a negative serum pregnancy test at screening and had a negative urine pregnancy test at all other time points). A woman was considered of childbearing potential unless she was permanently sterile (hysterectomy, bilateral salpingectomy, and bilateral oophorectomy) or was postmenopausal (had no menses for 12 months without an alternative medical cause and a serum follicle-stimulating hormone [FSH] concentration ≥40 International Units per Liter [IU/L])
  • Participants who did not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator or delegate at screening
  • Clinically significant abnormal clinical chemistry, haematology, or urinalysis as judged by the investigator. Participants with Gilbert's Syndrome were not allowed.
  • Participants with alanine aminotransferase (ALT) > 1.5 x upper limit of normal (ULN) at screening (Part 1 and Part 2) or Day -1 (Part 2 only)
  • Confirmed positive drugs of abuse test result
  • Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab), or human immunodeficiency virus (HIV) results
  • Evidence of renal impairment at screening, as indicated by an estimated creatinine clearance (CLcr) of <70 milliliters per minute (mL/min) using the Cockcroft-Gault equation
  • History of clinically significant cardiovascular, renal, hepatic, chronic respiratory, or gastrointestinal disease (including gall stones and/or cholecystectomy), or neurological or psychiatric disorder, as judged by the investigator
  • Serious adverse reaction or serious hypersensitivity to any drug or the IMP excipients
  • Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever was allowed unless it was active.
  • Donation or loss of greater than 400 mL of blood within the previous 3 months
  • Participants who were taking, or had taken, any prescribed or over-the-counter drug (other than 4 grams of paracetamol per day and/or hormone replacement therapy [HRT]) or herbal remedies in the 14 days before IMP administration. Exceptions may have applied on a case by case basis, if considered not to have interfered with the objectives of the study, as determined by the principal investigator.
  • Participants who had any ongoing fungal infections (stable toe nail onchomycosis was allowed)
  • Failure to satisfy the investigator of fitness to participate for any other reason

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Scienza basilare
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione sequenziale
  • Mascheramento: Triplicare

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: Part 1: Regimens AB(CD)
Participants received 50 milligrams (mg) BOS172767 E1 tablets or matching placebo (Regimen A) in the fasted state in Period 1, followed by 50 mg BOS172767 E2 tablets or matching placebo (Regimen B) in the fasted state in Period 2. In Period 3 and 4, participants received BOS172767-Ex (selected enantiomer from Part 1 [E1 or E2]) tablets or matching placebo (Regimens C and D, respectively) from Regimen A or B in the fasted state. The Period 3 and 4 dose was selected after review of data from Periods 1 and 2. In each Period, dosing occurred on Day 1, and there was a washout period of at least 10 days or 5 half-lives of the parent (whichever is greater) between each dose of investigational medicinal product.
Compresse orali
Oral tablets
Sperimentale: Part 1: Regimens BA(CD)
Participants received 50 milligrams (mg) BOS172767 E2 tablets or matching placebo (Regimen B) in the fasted state in Period 1, followed by 50 mg BOS172767 E1 tablets or matching placebo (Regimen A) in the fasted state in Period 2. In Period 3 and 4, participants received BOS172767-Ex (selected enantiomer from Part 1 [E1 or E2]) tablets or matching placebo (Regimens C and D, respectively) from Regimen A or B in the fasted state. The Period 3 and 4 dose was selected after review of data from Periods 1 and 2. In each Period, dosing occurred on Day 1, and there was a washout period of at least 10 days or 5 half-lives of the parent (whichever is greater) between each dose of investigational medicinal product.
Compresse orali
Oral tablets

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Part 1: Relative bioavailability of E1 versus E2 (Frel; exposure) of a single oral dose of BOS172767 enantiomer 1 (E1) and enantiomer 2 (E2) following administration to healthy participants based on Cmax, AUC(0-last), and AUC (0-inf)
Lasso di tempo: 24 hours post-dose for each of the four 6-day Periods
Cmax is defined as the maximum observed concentration. AUC(0-last) is defined as the area under the curve from 0 time to the last measurable concentration. AUC (0-inf) is defined as the area under the curve from 0 time extrapolated to infinity.
24 hours post-dose for each of the four 6-day Periods
Part 1: Number of participants with any treatment-emergent adverse event
Lasso di tempo: up to Day 6 of each Period; up to a 10-day Follow-up Period after last dose (up to Study Day 59)
up to Day 6 of each Period; up to a 10-day Follow-up Period after last dose (up to Study Day 59)
Part 1: Number of participants with abnormal, clinically significant physical examination findings
Lasso di tempo: up to Day 6 of each Period; up to a 10-day Follow-up Period after last dose (up to Study Day 59)
up to Day 6 of each Period; up to a 10-day Follow-up Period after last dose (up to Study Day 59)
Part 1: Number of participants with abnormal, clinically significant safety laboratory test findings
Lasso di tempo: up to Day 6 of each Period; up to a 10-day Follow-up Period after last dose (up to Study Day 59)
up to Day 6 of each Period; up to a 10-day Follow-up Period after last dose (up to Study Day 59)
Part 1: Number of participants with abnormal, clinically significant vital sign values
Lasso di tempo: up to Day 6 of each Period; up to a 10-day Follow-up Period after last dose (up to Study Day 59)
up to Day 6 of each Period; up to a 10-day Follow-up Period after last dose (up to Study Day 59)
Part 1: Number of participants with abnormal, clinically significant electrocardiogram findings
Lasso di tempo: up to Day 6 of each Period; up to a 10-day Follow-up Period after last dose (up to Study Day 59)
up to Day 6 of each Period; up to a 10-day Follow-up Period after last dose (up to Study Day 59)
Part 1: Plasma concentration of BOS172767 enantiomers 1 and 2
Lasso di tempo: 24 hours post-dose for each of the four 6-day Periods
24 hours post-dose for each of the four 6-day Periods
Part 1: Slope estimates (β) from the power model analysis on Cmax, AUC(0-last), and AUC(0-inf), as a measure of dose proportionality
Lasso di tempo: 24 hours post-dose for each of the four 6-day Periods
24 hours post-dose for each of the four 6-day Periods
Part 2: Plasma concentration of BOS172767-Ex (enantiomer E1 or E2)
Lasso di tempo: 24 hours post-dose
24 hours post-dose
Part 2: Number of participants with any treatment-emergent adverse event
Lasso di tempo: up to Day 24 of Part 2 (up to approximately 18 study weeks)
up to Day 24 of Part 2 (up to approximately 18 study weeks)
Part 2: Number of participants with abnormal, clinically significant physical examination findings
Lasso di tempo: up to Day 24 of Part 2 (up to approximately 18 study weeks)
up to Day 24 of Part 2 (up to approximately 18 study weeks)
Part 2: Number of participants with abnormal, clinically significant safety laboratory test findings
Lasso di tempo: up to Day 24 of Part 2 (up to approximately 18 study weeks)
up to Day 24 of Part 2 (up to approximately 18 study weeks)
Part 2: Number of participants with abnormal, clinically significant vital sign values
Lasso di tempo: up to Day 24 of Part 2 (up to approximately 18 study weeks)
up to Day 24 of Part 2 (up to approximately 18 study weeks)
Part 2: Number of participants with abnormal, clinically significant electrocardiogram findings
Lasso di tempo: up to Day 24 of Part 2 (up to approximately 18 study weeks)
up to Day 24 of Part 2 (up to approximately 18 study weeks)
Part 2: Slope estimates (β) from the power model analysis on Cmax, AUC(0-last), and AUC(0-inf), as a measure of dose proportionality
Lasso di tempo: 24 hours post-dose
24 hours post-dose

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Effettivo)

12 settembre 2019

Completamento primario (Effettivo)

22 gennaio 2020

Completamento dello studio (Effettivo)

22 gennaio 2020

Date di iscrizione allo studio

Primo inviato

12 agosto 2020

Primo inviato che soddisfa i criteri di controllo qualità

12 agosto 2020

Primo Inserito (Effettivo)

14 agosto 2020

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

18 novembre 2020

Ultimo aggiornamento inviato che soddisfa i criteri QC

17 novembre 2020

Ultimo verificato

1 novembre 2020

Maggiori informazioni

Termini relativi a questo studio

Altri numeri di identificazione dello studio

  • BOS172767-02
  • 2019-002289-11 (Numero EudraCT)
  • QSC201870 (Altro identificatore: Quotient Sciences)

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

NO

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

prodotto fabbricato ed esportato dagli Stati Uniti

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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