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T/QT Study to Investigate the Effect of Relacorilant on Cardiac Repolarization in Healthy Volunteers

10. september 2021 oppdatert av: Corcept Therapeutics

A Randomized, Partial Double-Blind, Placebo- and Positive- Controlled, Multiple-Dose, 4-Way Crossover, Thorough QT/QTc (TQT) Study to Investigate the Effect of Relacorilant on Cardiac Repolarization in Healthy Volunteers

This dedicated T/QT study will investigate the effect of relacorilant on cardiac repolarization in healthy participants.

Studieoversikt

Detaljert beskrivelse

This four-period crossover study with 12 treatment sequences includes relacorilant administered at therapeutic (400 mg once daily [QD]) and supra-therapeutic (800 mg QD) doses, placebo for relacorilant as a negative control, and oral moxifloxacin as a positive control. The positive control will serve to determine the sensitivity of the assay to detect small increases from baseline in the QTc interval. Each of the four treatment periods will last 5 days with a washout of at least 10 days between periods. Relacorilant and placebo to relacorilant will be administered double-blind; moxifloxacin will be administered open label.

Studietype

Intervensjonell

Registrering (Faktiske)

36

Fase

  • Fase 1

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

    • Missouri
      • Springfield, Missouri, Forente stater, 65802
        • Single Site

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år til 55 år (Voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

Inclusion Criteria:

  • Participant with a BMI ≥18.0 kg/m^2 and ≤30.0 kg/m^2 at screening
  • No clinically significant abnormal findings with the physical examination, medical/surgical/medication history, vital signs, or clinical laboratory assessments and adequate cardiac conduction by electrocardiogram (ECG) without evidence of first-, second- or third-degree atrioventricular block
  • Female participants of childbearing potential with a negative serum pregnancy test at screening and urine pregnancy test on Day -1 of Period 1
  • All male participants agree to use condom to prevent exposure to partner; male participants with female partner of childbearing potential to use a second method of contraception
  • Female participants of childbearing potential agree to use the highly effective contraception of low user dependency
  • Participant is willing and able to comply with all study procedures and restrictions
  • Participant understands the study procedures and agrees to participate by providing written informed consent.

Exclusion Criteria:

  • Participant with history or presence of any clinically significant cardiovascular, pulmonary, respiratory, hepatic, renal, hematological, endocrine, immunologic, dermatologic, neurological, psychiatric disease or disorder or any uncontrolled medical illness which in the opinion of the investigator would jeopardize the safety of the participant, interfere with study assessments, or impact the validity of the study results
  • Participant with a history or family history of additional risk factors for Torsade de Pointe (TdP)
  • Participant with a marked prolongation of ECG intervals, including QTcF >450 milliseconds (msec), PR >200 msec, or QRS >120 msec
  • Participant with resting heart rate of <45beats per minute (bpm) or >100 bpm
  • Participant with clinically significant abnormal ECG results
  • Participant who uses medications that could prolong the QT/QTc interval
  • Participant taking medications/dietary supplements that are highly dependent on cytochrome (CYP)3A for clearance and cannot undergo dose modification upon co-administration with strong CYP3A inhibitors
  • Participant using any strong CYP3A inhibitor/inducer or any other medications prohibited per protocol
  • Participant who is receiving testosterone within 40 days prior to study start
  • Participant with a positive result for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen, or hepatitis C antibody
  • Participant with a positive test result for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) viral RNA test, either asymptomatic or present with symptoms of Coronavirus disease 2019 (COVID-19)
  • Participant who has travelled abroad within 3 months prior to the screening visit or plans to travel abroad during the study
  • Participant who has had a major surgery within the last 28 days prior to Screening
  • Participant who received any investigational product within 30 days prior to Screening
  • Participant who has a known or suspected allergy, or sensitivity to study products, or any of its ingredient(s), or to moxifloxacin
  • Intolerance to repeated venipuncture or inability to swallow capsules
  • Donation of blood within 56 days or plasma within 14 days prior to Screening or plans to donate during the entire study period
  • Positive alcohol test and/or positive drugs of abuse screen or reports of a history of substance or alcohol abuse within 1 year prior to Screening
  • Female participant who is pregnant, breastfeeding, or is planning to become pregnant during the entire study period
  • Male participant with pregnant partner.

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Randomisert
  • Intervensjonsmodell: Crossover-oppdrag
  • Masking: Dobbelt

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Treatment Sequence 1
Participants will receive relacorilant 400 mg once daily (QD) for 5 days in Period 1, followed by relacorilant 800 mg QD for 5 days in Period 2, followed by placebo to relacorilant QD for 5 days in Period 3, followed by placebo to relacorilant QD for 4 days and moxifloxacin 400 mg on Day 5 in Period 4. Treatment periods will be separated by a washout of at least 10 days.
Relacorilant 400 mg (therapeutic dose) or 800 mg (supra-therapeutic dose) capsule by mouth once daily
Andre navn:
  • CORT125134
Placebo to relacorilant capsule by mouth once daily
Moxifloxacin 400 mg tablet by mouth
Eksperimentell: Treatment Sequence 2
Participants will receive relacorilant 800 mg QD for 5 days in Period 1, followed by placebo to relacorilant QD for 4 days and moxifloxacin 400 mg on Day 5 in Period 2, followed by relacorilant 400 mg QD for 5 days in Period 3, followed by placebo to relacorilant QD for 5 days in Period 4. Treatment periods will be separated by a washout of at least 10 days.
Relacorilant 400 mg (therapeutic dose) or 800 mg (supra-therapeutic dose) capsule by mouth once daily
Andre navn:
  • CORT125134
Placebo to relacorilant capsule by mouth once daily
Moxifloxacin 400 mg tablet by mouth
Eksperimentell: Treatment Sequence 3
Participants will receive placebo to relacorilant QD for 5 days in Period 1, followed by relacorilant 400 mg QD for 5 days in Period 2, followed by placebo to relacorilant QD for 4 days and moxifloxacin 400 mg on Day 5 in Period 3, followed by relacorilant 800 mg QD for 5 days in Period 4. Treatment periods will be separated by a washout of at least 10 days.
Relacorilant 400 mg (therapeutic dose) or 800 mg (supra-therapeutic dose) capsule by mouth once daily
Andre navn:
  • CORT125134
Placebo to relacorilant capsule by mouth once daily
Moxifloxacin 400 mg tablet by mouth
Eksperimentell: Treatment Sequence 4
Participants will receive relacorilant QD for 4 days and moxifloxacin 400 mg on Day 5 in Period 1, followed by placebo to relacorilant QD for 5 days in Period 2, followed by relacorilant 800 mg QD for 5 days in Period 3, followed by relacorilant 400 mg QD for 5 days in Period 4. Treatment periods will be separated by a washout of at least 10 days.
Relacorilant 400 mg (therapeutic dose) or 800 mg (supra-therapeutic dose) capsule by mouth once daily
Andre navn:
  • CORT125134
Placebo to relacorilant capsule by mouth once daily
Moxifloxacin 400 mg tablet by mouth
Eksperimentell: Treatment Sequence 5
Participants will receive relacorilant 800 mg QD for 5 days in Period 1, followed by placebo to relacorilant QD for 5 days in Period 2, followed by relacorilant 400 mg QD for 5 days in Period 3, followed by relacorilant QD for 4 days and moxifloxacin 400 mg on Day 5 in Period 4. Treatment periods will be separated by a washout of at least 10 days.
Relacorilant 400 mg (therapeutic dose) or 800 mg (supra-therapeutic dose) capsule by mouth once daily
Andre navn:
  • CORT125134
Placebo to relacorilant capsule by mouth once daily
Moxifloxacin 400 mg tablet by mouth
Eksperimentell: Treatment Sequence 6
Participants will receive placebo to relacorilant QD for 5 days in Period 1, followed by placebo to relacorilant QD for 4 days and moxifloxacin 400 mg on Day 5 in Period 2, followed by relacorilant 800 mg QD for 5 days in Period 3, followed by relacorilant 400 mg QD for 5 days in Period 4. Treatment periods will be separated by a washout of at least 10 days.
Relacorilant 400 mg (therapeutic dose) or 800 mg (supra-therapeutic dose) capsule by mouth once daily
Andre navn:
  • CORT125134
Placebo to relacorilant capsule by mouth once daily
Moxifloxacin 400 mg tablet by mouth
Eksperimentell: Treatment Sequence 7
Participants will receive relacorilant 400 mg QD for 5 days in Period 1, followed by relacorilant 800 mg QD for 5 days in Period 2, followed by placebo to relacorilant QD for 4 days and moxifloxacin 400 mg on Day 5 in Period 3, followed by placebo to relacorilant QD for 5 days in Period 4. Treatment periods will be separated by a washout of at least 10 days.
Relacorilant 400 mg (therapeutic dose) or 800 mg (supra-therapeutic dose) capsule by mouth once daily
Andre navn:
  • CORT125134
Placebo to relacorilant capsule by mouth once daily
Moxifloxacin 400 mg tablet by mouth
Eksperimentell: Treatment Sequence 8
Participants will receive placebo to relacorilant QD for 4 days and moxifloxacin 400 mg on Day 5 in Period 1, followed by relacorilant 400 mg QD for 5 days in Period 2, followed by placebo to relacorilant QD for 5 days in Period 3, followed by relacorilant 800 mg QD for 5 days in Period 4. Treatment periods will be separated by a washout of at least 10 days.
Relacorilant 400 mg (therapeutic dose) or 800 mg (supra-therapeutic dose) capsule by mouth once daily
Andre navn:
  • CORT125134
Placebo to relacorilant capsule by mouth once daily
Moxifloxacin 400 mg tablet by mouth
Eksperimentell: Treatment Sequence 9
Participants will receive placebo to relacorilant QD for 5 days in Period 1, followed by relacorilant 400 mg QD for 5 days in Period 2, followed by relacorilant 800 mg QD for 5 days in Period 3, followed by placebo to relacorilant QD for 4 days and moxifloxacin 400 mg on Day 5 in Period 4. Treatment periods will be separated by a washout of at least 10 days.
Relacorilant 400 mg (therapeutic dose) or 800 mg (supra-therapeutic dose) capsule by mouth once daily
Andre navn:
  • CORT125134
Placebo to relacorilant capsule by mouth once daily
Moxifloxacin 400 mg tablet by mouth
Eksperimentell: Treatment Sequence 10
Participants will receive relacorilant 400 mg QD for 5 days in Period 1, followed by placebo to relacorilant QD for 4 days and moxifloxacin 400 mg on Day 5 in Period 2, followed by placebo to relacorilant QD for 5 days in Period 3, followed by relacorilant 800 mg QD for 5 days in Period 4. Treatment periods will be separated by a washout of at least 10 days.
Relacorilant 400 mg (therapeutic dose) or 800 mg (supra-therapeutic dose) capsule by mouth once daily
Andre navn:
  • CORT125134
Placebo to relacorilant capsule by mouth once daily
Moxifloxacin 400 mg tablet by mouth
Eksperimentell: Treatment Sequence 11
Participants will receive relacorilant 800 mg QD for 5 days in Period 1, followed by placebo to relacorilant QD for 5 days in Period 2, followed by placebo to relacorilant QD for 4 days and moxifloxacin 400 mg on Day 5 in Period 3, followed by relacorilant 400 mg QD for 5 days in Period 4. Treatment periods will be separated by a washout of at least 10 days.
Relacorilant 400 mg (therapeutic dose) or 800 mg (supra-therapeutic dose) capsule by mouth once daily
Andre navn:
  • CORT125134
Placebo to relacorilant capsule by mouth once daily
Moxifloxacin 400 mg tablet by mouth
Eksperimentell: Treatment Sequence 12
Participants will receive placebo to relacorilant QD for 4 days and moxifloxacin 400 mg on Day 5 in Period 1, followed by relacorilant 800 mg QD for 5 days in Period 2, followed by relacorilant 400 mg QD for 5 days in Period 3, followed by placebo to relacorilant QD for 5 days in Period 4. Treatment periods will be separated by a washout of at least 10 days.
Relacorilant 400 mg (therapeutic dose) or 800 mg (supra-therapeutic dose) capsule by mouth once daily
Andre navn:
  • CORT125134
Placebo to relacorilant capsule by mouth once daily
Moxifloxacin 400 mg tablet by mouth

Hva måler studien?

Primære resultatmål

Resultatmål
Tidsramme
Placebo-corrected Change from Baseline in Cardiac QT Interval Corrected by Fridericia's Formula (QTcF)
Tidsramme: Before dosing (Baseline) through 24 hours after the final dose on Day 5 in each treatment period
Before dosing (Baseline) through 24 hours after the final dose on Day 5 in each treatment period

Sekundære resultatmål

Resultatmål
Tidsramme
Change from Baseline in Cardiac QTcF
Tidsramme: Before dosing (Baseline) through 24 hours after the final dose on Day 5 in each treatment period
Before dosing (Baseline) through 24 hours after the final dose on Day 5 in each treatment period
Change from Baseline in Heart Rate (HR)
Tidsramme: Before dosing (Baseline) through 24 hours after the final dose on Day 5 in each treatment period
Before dosing (Baseline) through 24 hours after the final dose on Day 5 in each treatment period
Placebo-corrected Change from Baseline in HR
Tidsramme: Before dosing (Baseline) through 24 hours after the final dose on Day 5 in each treatment period
Before dosing (Baseline) through 24 hours after the final dose on Day 5 in each treatment period
Change from Baseline in Cardiac PR Interval
Tidsramme: Before dosing (Baseline) through 24 hours after the final dose on Day 5 in each treatment period
Before dosing (Baseline) through 24 hours after the final dose on Day 5 in each treatment period
Placebo-corrected Change from Baseline in Cardiac PR Interval
Tidsramme: Before dosing (Baseline) through 24 hours after the final dose on Day 5 in each treatment period
Before dosing (Baseline) through 24 hours after the final dose on Day 5 in each treatment period
Change from Baseline in Cardiac QRS Intervals
Tidsramme: Before dosing (Baseline) through 24 hours after the final dose on Day 5 in each treatment period
Before dosing (Baseline) through 24 hours after the final dose on Day 5 in each treatment period
Placebo-corrected Change from Baseline in Cardiac QRS Intervals
Tidsramme: Before dosing (Baseline) through 24 hours after the final dose on Day 5 in each treatment period
Before dosing (Baseline) through 24 hours after the final dose on Day 5 in each treatment period
Number of Participants with a Categorical Outlier in QTcF
Tidsramme: Up to Day 6 in each treatment period (through 24 hours after the final dose on Day 5 in each treatment period)
Up to Day 6 in each treatment period (through 24 hours after the final dose on Day 5 in each treatment period)
Number of Participants with a Categorical Outlier in HR
Tidsramme: Up to Day 6 in each treatment period (through 24 hours after the final dose on Day 5 in each treatment period)
Up to Day 6 in each treatment period (through 24 hours after the final dose on Day 5 in each treatment period)
Number of Participants with a Categorical Outlier in PR Interval
Tidsramme: Up to Day 6 in each treatment period (through 24 hours after the final dose on Day 5 in each treatment period)
Up to Day 6 in each treatment period (through 24 hours after the final dose on Day 5 in each treatment period)
Number of Participants with a Categorical Outlier in QRS Intervals
Tidsramme: Up to Day 6 in each treatment period (through 24 hours after the final dose on Day 5 in each treatment period)
Up to Day 6 in each treatment period (through 24 hours after the final dose on Day 5 in each treatment period)
Number of Participants with a Treatment-emergent Change of T-wave Morphology
Tidsramme: Up to Day 6 in each treatment period (through 24 hours after the final dose on Day 5 in each treatment period)
Up to Day 6 in each treatment period (through 24 hours after the final dose on Day 5 in each treatment period)
Number of Participants with a Treatment-emergent Presence of U-waves
Tidsramme: Up to Day 6 in each treatment period (through 24 hours after the final dose on Day 5 in each treatment period)
Up to Day 6 in each treatment period (through 24 hours after the final dose on Day 5 in each treatment period)
Maximum Plasma Concentration (Cmax) of Relacorilant, Metabolites of Relacorilant, and Moxifloxacin
Tidsramme: Before dosing and at 0.5, 1, 1,5, 2, 3, 4, 6, 8, 12, 16, and 24 hours after dosing on Day 1 and 5 in each treatment period
Before dosing and at 0.5, 1, 1,5, 2, 3, 4, 6, 8, 12, 16, and 24 hours after dosing on Day 1 and 5 in each treatment period
Time to Reach Cmax (Tmax) of Plasma Relacorilant, Metabolites of Relacorilant, and Moxifloxacin
Tidsramme: Before dosing and at 0.5, 1, 1,5, 2, 3, 4, 6, 8, 12, 16, and 24 hours after dosing on Day 1 and 5 in each treatment period
Before dosing and at 0.5, 1, 1,5, 2, 3, 4, 6, 8, 12, 16, and 24 hours after dosing on Day 1 and 5 in each treatment period
Minimum Plasma Concentration (Cmin) of Relacorilant, Metabolites of Relacorilant, and Moxifloxacin
Tidsramme: Before dosing on Day 5 of each treatment period
Before dosing on Day 5 of each treatment period
Area Under the Plasma-concentration Curve from Time Zero to Time of Last Measurable Concentration (AUClast) of Relacorilant, Metabolites of Relacorilant, and Moxifloxacin
Tidsramme: Before dosing and at 0.5, 1, 1,5, 2, 3, 4, 6, 8, 12, 16, and 24 hours after dosing on Day 1 and 5 in each treatment period
Before dosing and at 0.5, 1, 1,5, 2, 3, 4, 6, 8, 12, 16, and 24 hours after dosing on Day 1 and 5 in each treatment period
Area Under the Plasma-concentration Curve from Time Zero to 24 Hours Postdose (AUC0-24) of Relacorilant, Metabolites of Relacorilant, and Moxifloxacin
Tidsramme: Before dosing and at 0.5, 1, 1,5, 2, 3, 4, 6, 8, 12, 16, and 24 hours after dosing on Day 1 and 5 in each treatment period
Before dosing and at 0.5, 1, 1,5, 2, 3, 4, 6, 8, 12, 16, and 24 hours after dosing on Day 1 and 5 in each treatment period
Number of Participants with One or More Adverse Events
Tidsramme: Up to Day 6 in each treatment period (up to 51 days)
Up to Day 6 in each treatment period (up to 51 days)
Number of Participants Discontinued From Study Treatment due to an Adverse Event
Tidsramme: Up to Day 6 of each treatment period (up to 51 days)
Up to Day 6 of each treatment period (up to 51 days)

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

22. januar 2021

Primær fullføring (Faktiske)

17. mai 2021

Studiet fullført (Faktiske)

13. juli 2021

Datoer for studieregistrering

Først innsendt

29. januar 2021

Først innsendt som oppfylte QC-kriteriene

11. mars 2021

Først lagt ut (Faktiske)

12. mars 2021

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

14. september 2021

Siste oppdatering sendt inn som oppfylte QC-kriteriene

10. september 2021

Sist bekreftet

1. september 2021

Mer informasjon

Begreper knyttet til denne studien

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

Nei

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Ja

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

produkt produsert i og eksportert fra USA

Nei

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

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