- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT01998672
Multiple Ascending Oral Dose Phase I Study With Px-102
3. november 2014 oppdatert av: Phenex Pharmaceuticals AG
A Double-blind, Randomised, Placebo-controlled, Dose-escalation Study of the Safety, Tolerability and Pharmacokinetics of Increasing Multiple Oral Doses of Px-102 to Healthy Subjects
The purpose of this study is to assess the safety and tolerability of the FXR agonist Px-102 in healthy subjects after 7 days multiple oral dosing.
Studieoversikt
Detaljert beskrivelse
The study is a single-centre, double-blind, randomized, placebo-controlled, parallel group phase I study with healthy male subjects receiving ascending multiple oral oral doses of Px-102 to assess the safety and tolerability, pharmacokinetics and pharmacodynamics.
Studietype
Intervensjonell
Registrering (Faktiske)
42
Fase
- Fase 1
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
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Neuss, Tyskland
- FOCUS Clinical Drug Development GmbH
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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 45 år (Voksen)
Tar imot friske frivillige
Ja
Kjønn som er kvalifisert for studier
Mann
Beskrivelse
Inclusion Criteria:
- Healthy male subject of Caucasian origin 18 to 45 years of age (inclusive).
- Good state of health (mentally and physically) as determined by medical history, physical examination, vital signs, ECG recording and clinical lab results.
- BMI in between 20-29 kg/m² (inclusive); with absolute weight in between 70 to 120 kg.
- Total cholesterol and liver enzyme levels [alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), alkaline phosphatase (AP)] strictly within the normal ranges at screening and on Day -1. Serum triglyceride not exceeding the upper limit of normal range.
- HbA1c ≤ 6.5%
- Subject has been informed both verbally and in writing and has given written consent to participation in the study prior to start and any study-related procedure.
- Negative results for HIV- and Hepatitis-B and -C serology at screening.
- Subject (including female partners of childbearing potential) has to use a highly effective method of birth control (failure rate less than 1% per year when used consistently and correctly), e.g. implants, injectables, combined oral contra-ceptives in combination with a barrier method, some intrauterine contraceptive devices or sexual abstinence.
Exclusion Criteria:
- Female gender
- Use of prescription or non-prescription drugs within 7 days (30 if the drug is a possible enzyme inducer) prior to administration of study medication. Use of drugs known to induce steatosis (e.g. valproate, amiodarone or prednisone) or to affect body weight and carbohydrate metabolism
- Any acute or chronic illness or clinically relevant finding at screening and at base-line examination which may jeopardize the subject's participation in the study
- History or presence of biliary obstruction or biliary disease, hepatic encephalopathy, advanced ascites, portal hypertension, esophageal/gastric variceal bleeding, hepatocellular carcinoma, previous liver transplantation or any other chronic liver disease
- Renal dysfunction, e.g. glomerular filtration rate ≤ 80 ml/min/1.73 m2 (as determined by the formula of Cockroft-Gault)
- Type I or II Diabetes
- Any clinically relevant abnormality on screening medical assessment, laboratory examination, 12-lead ECG
- Any clinically relevant finding in the baseline telemetry within the pre-dose evaluated observation period of at least 20 hours
- Marked baseline prolongation of QT/QTc interval (QTc interval > 440 ms) in the 12-lead ECG using the Fridericia method for QTc analysis
- Heart rate < 50 bpm.
- History of pathological cardiovascular symptoms or a severe cardiovascular event
- History of severe chronic autoimmune diseases such as severe allergy, atopic eczema, chronic dermatitis, severe psoriasis, multiple sclerosis, severe asthma, lupus or related disorders
- Allergies (except for mild forms of hay fever) or history of hypersensitivity reactions
- Smoking (regular or irregular) > 5 cigarettes (or equivalent) per day
- Excessive alcohol drinking (more than approximately 20 g alcohol per day), unable to refrain from alcohol drinking from 48 hours prior to dosing until the last pharmacokinetic blood sample has been withdrawn
- Positive test for drugs or alcohol at screening or prior to the dosing session
- History of alcoholism or drug/chemical/substance abuse within past 2 years
- Investigator deems the subject unable or unwilling to comply fully with the study protocol
- Has received clinical study medication within the last 30 days prior to this study
- Donation or loss of 400 ml or more of blood within eight (8) weeks prior to dosing
- Allergic to any of the active or inactive ingredients in the study medication
- Any other reason which the Investigator considers unsuitable for the subject to participate
- Any condition or previous disease leading to pruritus or itching of the skin.
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: Parallell tildeling
- Masking: Trippel
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
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Aktiv komparator: Px-102
Px-102 drinking solution, 0.5 mg/kg, 1.0 mg/kg and 1.5 mg/kg
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Px-102 drinking solution, 0.5 mg/kg, 1.0 mg/kg and 1.5 mg/kg
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Placebo komparator: Placebo
Oral drinking solution
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Drinking solution
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
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Safety and tolerability of Px-102
Tidsramme: 7 days
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Adverse event monitoring, laboratory values, cardiovascular monitoring.
Comparison active vs. placebo
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7 days
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Pharmacokinetics of Px-102 and metabolites
Tidsramme: Day 1: 0 min, 15 min, 30 min, 60 min, 1.5 h, 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 8 h, 12 h, 22 h, 24 h; Day 5 and 6: pre-dose; Day 7: 0 min, 15 min, 30 min, 60 min, 1.5 h, 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 8 h, 12 h, 22 h, 24 h, 30 h.
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Plasma, urine and fecal concentrations (ng/mL) of Px-102 and metabolites measured by LC-MS/MS.
AUC, Cmax and other pk parameters.
Comparison of the pk data on day 7 vs. day 1
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Day 1: 0 min, 15 min, 30 min, 60 min, 1.5 h, 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 8 h, 12 h, 22 h, 24 h; Day 5 and 6: pre-dose; Day 7: 0 min, 15 min, 30 min, 60 min, 1.5 h, 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 8 h, 12 h, 22 h, 24 h, 30 h.
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Pharmacodynamics
Tidsramme: Pre-dose, 1, 2, 4, 8 and 10 hours after administration on Days 1 and 7; Pre-dose, 2 hours and 8 hours after administration on Days 2 to 6; at 22 hours after the last administration
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Markers for FXR activation (e.G.
FGF19 (pg/mL) measurement by ELISA).
Comparison active vs. placebo
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Pre-dose, 1, 2, 4, 8 and 10 hours after administration on Days 1 and 7; Pre-dose, 2 hours and 8 hours after administration on Days 2 to 6; at 22 hours after the last administration
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Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Etterforskere
- Studiestol: Claus Kremoser, Dr., Phenex Pharmaceuticals AG
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
1. februar 2012
Primær fullføring (Faktiske)
1. oktober 2012
Studiet fullført (Faktiske)
1. oktober 2012
Datoer for studieregistrering
Først innsendt
19. november 2013
Først innsendt som oppfylte QC-kriteriene
25. november 2013
Først lagt ut (Anslag)
2. desember 2013
Oppdateringer av studieposter
Sist oppdatering lagt ut (Anslag)
4. november 2014
Siste oppdatering sendt inn som oppfylte QC-kriteriene
3. november 2014
Sist bekreftet
1. november 2014
Mer informasjon
Begreper knyttet til denne studien
Andre studie-ID-numre
- PHS-Px-102-I-02
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. .