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3-Way Crossover Study to Compare the PK (Pharmokinetics) and to Evaluate the Effect of Food on the Bioavailability

10. mars 2022 oppdatert av: Chengdu SciMount Pharmatech Co., Ltd.

A Phase 1, Randomized, Open-Label, Single-Dose, 3-Way Crossover Study to Compare the PK of Two Oral Formulations of SMP-100 and to Evaluate the Effect of Food on the Bioavailability of SMP-100 Tablets in Normal Healthy Volunteers

This is a single center, Phase 1, randomized, open-label, single-dose, 3 treatment, 3-period, 6-sequence, crossover study designed to compare the PK of SMP-100 dissolved in water for oral administration with SMP-100 tablets under fasting conditions, and to evaluate the effect of food on the bioavailability of SMP-100 tablets in healthy subjects.

Studieoversikt

Status

Fullført

Intervensjon / Behandling

Detaljert beskrivelse

SMP-100 is a novel serotonin receptor 3 (5-HT3) partial agonist. The compound is under development in an oral dosage form for the treatment of diarrhea-predominant irritable bowel syndrome (IBS-d). The study drug also has the potential to treat chemotherapy induced nausea and emesis and diarrhea due to carcinoid syndrome.

A single ascending dose (SAD) and multiple ascending dose (MAD) clinical study (study number SMP-100-101) evaluating the safety, tolerability, and PK profile of orally administered SMP-100 in healthy volunteers is ongoing. Regarding safety, there have been no clinically relevant abnormal vital signs, ECGs, laboratory results or SAEs.

In each period, subjects will receive a single 4 mg dose of SMP-100 on Day 1 (Period 1), Day 4 (Period 2), and Day 7 (Period 3), under fasting or fed conditions, followed by 48 hours of PK and safety assessments.

The study will include a screening visit from Day -28 to Day -2. Eligible subjects will be admitted to the clinical site on Day -1 and will be confined until completion of the assessments on Day 9. There will be a washout period of at least 72 hours between doses.

Primary objectives:

  • To compare the PK of SMP-100 dissolved in water for oral administration with SMP-100 tablets under fasting conditions, following a single dose in healthy subjects.
  • To evaluate the effect of a high-fat, high-calorie meal on the bioavailability of SMP-100 tablets, following a single dose in healthy subjects.

Secondary objective:

• To evaluate the safety and tolerability of two SMP-100 oral formulations when administered to healthy subjects.

Studietype

Intervensjonell

Registrering (Faktiske)

8

Fase

  • Fase 1

Kontakter og plasseringer

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

Studiesteder

      • Adelaide, Australia, SA 5000
        • CMAX Clinical Research Pty Ltd

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 59 år (Voksen)

Tar imot friske frivillige

Ja

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

Inclusion Criteria:

  1. Male or female, non-smoker (no use of tobacco or nicotine products within 3 months prior to screening), ≥18 and ≤59 years old at time of screening.
  2. Body mass index (BMI) >18.5 and <30.0 kg/m2 and body weight ≥50.0 kg for males and ≥45.0 kg for females.
  3. Healthy as defined by:

    1. the absence of clinically significant illness and surgery within 4 weeks prior to dosing.
    2. the absence of clinically significant history of neurological, endocrine, cardiovascular, respiratory, hematological, immunological, psychiatric, gastrointestinal, renal, hepatic, and metabolic disease.
    3. the absence of clinically significant history of constipation, diarrhea, or irregular bowel transit in the last 4 weeks.
    4. the absence of clinically significant history of irritable bowel syndrome (IBS) of any type.
    5. the absence of current or history of ischemic colitis.
    6. the absence of any other gastrointestinal disease which could interfere with the absorption of orally-administered medication.
  4. Female subjects of non-childbearing potential must be:

    1. post-menopausal (spontaneous amenorrhea for at least 12 months prior to dosing) with confirmation by documented follicle-stimulating hormone (FSH) levels ≥40 mIU/mL at screening; or
    2. surgically sterile (bilateral oophorectomy, hysterectomy or tubal ligation at least 3 months prior to dosing).
  5. Sexually active female subjects of childbearing potential and non-sterile male subjects must be willing to use an acceptable contraceptive method throughout the study as detailed in section 11.1.
  6. Willing to take off dentures or mouth piercing at the time of dosing (for Treatment A).
  7. Able to understand the study procedures and provide signed informed consent form (ICF) to participate in the study.

Exclusion Criteria:

  1. Any clinically significant (in the opinion of the Investigator) abnormal finding at physical examination at screening.
  2. Any clinically significant (in the opinion of the Investigator) abnormal laboratory test results or positive serology test results for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) antigen and antibody at screening.
  3. Positive pregnancy test or lactating female subject.
  4. Positive urine drug screen, urine cotinine test, or alcohol breath test at screening or Day -1.
  5. Known allergic reactions to any excipient in the formulations.
  6. History of hypersensitivity to 5-hydroxytryptamine 3 receptor (5-HT3) receptor antagonists or agonists.
  7. Clinically significant ECG abnormalities (Fridericia's corrected QT interval [QTcF] >450 ms for males and >470 ms for females).
  8. Clinically significant vital signs abnormalities (systolic BP lower than 90 or over 160 mmHg, diastolic BP lower than 50 or over 95 mmHg, or HR less than 45 bpm) at screening.
  9. Clinically significant orthostatic vital signs abnormalities such as decrease in systolic BP of 20 mmHg or higher, decrease in diastolic BP of 10 mmHg or higher, or increase in HR of 30 bpm or higher within 3 minutes after passing from a supine to a standing position.
  10. History of significant drug abuse within 1 year prior to screening or use of drugs such as marijuana within 3 months prior to the screening visit or drugs such as cocaine, phencyclidine (PCP), crack, opioid derivatives including heroin, and amphetamine derivatives within 1 year prior to screening.
  11. History of significant alcohol abuse within 1 year prior to screening or regular use of alcohol within 6 months prior to the screening visit that exceeds 14 units of alcohol per week (1 unit = 150 mL of wine, 375 mL of mid strength beer, or 30 mL of distilled alcohol 40%).
  12. Use of medications within the timeframes specified in section 11.2.
  13. Participation in a clinical research study involving the administration of an investigational or marketed drug or device within 30 days prior to dosing or of a biological product within 90 days prior to dosing.
  14. Previous participation in a clinical research study involving the administration of SMP-100.
  15. Donation of plasma within 7 days prior to dosing or donation or loss of 500 mL or more of whole blood within 8 weeks prior to dosing.
  16. Presence of orthodontic braces or orthodontic retention wires, or any physical findings in the mouth or tongue that would be likely to interfere with successful completion of the dosing procedure.
  17. Any reason which, in the opinion of the Investigator, would prevent the subject from participating in the study.

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: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Treatment A: SMP-100 dissolved in water administered under fasting conditions
12 subjects,For Treatment A, SMP-100 will be dissolved in a total of 240 mL of water and administered orally to each subjects, and a hand and mouth check will be performed to ensure consumption of the medication. Subjects will be required not to wear dentures or mouth piercing at the time of dosing. No food will be allowed from at least 10 hours before dosing until at least 4 hours post-dose.
In each period, subjects will receive a single dose of SMP-100 on Day 1 (Period 1), Day 4 (Period 2), and Day 7 (Period 3), under fasting or fed conditions, followed by 48 hours of PK and safety assessments.
Andre navn:
  • SMP-100 mikstur
  • ALB-137391(a)
  • CSTI-300
  • SMP-100 tablet
Eksperimentell: Treatment B: SMP-100 tablets administered under fasting conditions
12 subjects,For Treatment B, SMP-100 tablets will be administered to each subject with 240 mL of water and a hand and mouth check will be performed to ensure consumption of the medication. The dosing procedure must be completed within 2 minutes. In the event that subjects cannot swallow all tablets with 240 mL of water, additional water may be allowed up to a maximum total volume of 400 mL. No food will be allowed from at least 10 hours before dosing until at least 4 hours post-dose.
In each period, subjects will receive a single dose of SMP-100 on Day 1 (Period 1), Day 4 (Period 2), and Day 7 (Period 3), under fasting or fed conditions, followed by 48 hours of PK and safety assessments.
Andre navn:
  • SMP-100 mikstur
  • ALB-137391(a)
  • CSTI-300
  • SMP-100 tablet
Eksperimentell: Treatment C: SMP-100 tablets administered under fed conditions

12 subjects,For Treatment C, SMP-100 tablets will be administered to each subject with 240 mL of water and a hand and mouth check will be performed to ensure consumption of the medication. The dosing procedure must be completed within 2 minutes. In the event that subjects cannot swallow all tablets with 240 mL of water, additional water may be allowed up to a maximum total volume of 400 mL.

After a supervised fast of at least 10 hours, subjects will be served a high-fat, high-calorie meal of approximately 800 to 1000 calories (approximately 50% of total caloric content of the meal derived from fat). This test meal should derive approximately 150, 250, and 500-600 calories from protein, carbohydrate, and fat, respectively. Subjects should start the meal approximately 30 minutes prior to drug administration. Subjects will be required to completely eat the meal in 30 minutes or less. No food will be allowed until at least 4 hours post-dose.

In each period, subjects will receive a single dose of SMP-100 on Day 1 (Period 1), Day 4 (Period 2), and Day 7 (Period 3), under fasting or fed conditions, followed by 48 hours of PK and safety assessments.
Andre navn:
  • SMP-100 mikstur
  • ALB-137391(a)
  • CSTI-300
  • SMP-100 tablet

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Primary PK endpoints: AUC( 0-inf)
Tidsramme: pre-dose and 0.25, 0.5, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, and 48 hours post-dose
Area under the concentration-time curve from time zero to infinity (extrapolated)
pre-dose and 0.25, 0.5, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, and 48 hours post-dose
Primary PK endpoint: AUC(0-t)
Tidsramme: pre-dose and 0.25, 0.5, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, and 48 hours post-dose
Area under the concentration-time curve from time zero until the last observed concentration
pre-dose and 0.25, 0.5, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, and 48 hours post-dose
Primary PK endpoint: Cmax
Tidsramme: pre-dose and 0.25, 0.5, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, and 48 hours post-dose
Maximal observed concentration
pre-dose and 0.25, 0.5, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, and 48 hours post-dose

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Secondary PK endpoint: Tmax
Tidsramme: pre-dose and 0.25, 0.5, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, and 48 hours post-dose
Time when the maximal concentration is observed
pre-dose and 0.25, 0.5, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, and 48 hours post-dose
Secondary PK endpoint: Tlag
Tidsramme: pre-dose and 0.25, 0.5, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, and 48 hours post-dose
Time of observation prior to the first observation with a measurable (non-zero)
pre-dose and 0.25, 0.5, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, and 48 hours post-dose
Secondary PK endpoint: T½ el
Tidsramme: pre-dose and 0.25, 0.5, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, and 48 hours post-dose
Terminal elimination half-life
pre-dose and 0.25, 0.5, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, and 48 hours post-dose
Secondary PK endpoint: Kel
Tidsramme: pre-dose and 0.25, 0.5, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, and 48 hours post-dose
Elimination rate constant
pre-dose and 0.25, 0.5, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, and 48 hours post-dose
Secondary PK endpoint: Cl/F
Tidsramme: pre-dose and 0.25, 0.5, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, and 48 hours post-dose
Apparent body clearance
pre-dose and 0.25, 0.5, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, and 48 hours post-dose
Secondary PK endpoint: Vz/F
Tidsramme: pre-dose and 0.25, 0.5, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, and 48 hours post-dose
Apparent volume of distribution
pre-dose and 0.25, 0.5, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, and 48 hours post-dose
Adverse event profile
Tidsramme: Day -1 to Day 9
Nature, incidence and severity of treatment-emergent adverse events
Day -1 to Day 9

Samarbeidspartnere og etterforskere

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

Etterforskere

  • Hovedetterforsker: Thomas Polasek, CMAX Clinical Research Pty Ltd

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)

9. september 2021

Primær fullføring (Faktiske)

30. november 2021

Studiet fullført (Faktiske)

10. desember 2021

Datoer for studieregistrering

Først innsendt

22. august 2021

Først innsendt som oppfylte QC-kriteriene

26. august 2021

Først lagt ut (Faktiske)

31. august 2021

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

11. mars 2022

Siste oppdatering sendt inn som oppfylte QC-kriteriene

10. mars 2022

Sist bekreftet

1. august 2021

Mer informasjon

Begreper knyttet til denne studien

Andre studie-ID-numre

  • SciMount

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Ja

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

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