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A Study to Assess the Safety, Tolerability and Effects of Single and Multiple Ascending Doses of ASP1707 in Healthy Male and Pre-menopausal Female Subjects, Including a Comparison of the Effects Under Fasted and Fed Conditions in Healthy Young Male Subjects

17 febbraio 2015 aggiornato da: Astellas Pharma Europe B.V.

A Double Blind, Randomized, Placebo-controlled, Ascending Single and Multiple Oral Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ASP1707 in Healthy Young and Elderly Male Subjects and in Healthy Pre-menopausal Female Subjects Including an Open-label Comparison of Pharmacokinetics Under Fasted and Fed Conditions in Healthy Young Male Subjects

This study consists of four parts:

Part 1 is a randomized, double-blind, placebo-controlled, single ascending dose study in healthy young male subjects to evaluate the safety, tolerability pharmacokinetics (PK) and effect on certain hormones and if possible to determine the highest well-tolerated dose of ASP1707 in healthy young male subjects under fasted conditions.

Part 2 is an open label, randomized crossover, single dose study to determine the effect of food on the pharmacokinetics of ASP1707and effect on certain hormones in healthy young male subjects.

Part 3 is a randomized, double-blind, placebo-controlled, multiple ascending dose study to evaluate the safety, tolerability and pharmacokinetics (PK) of ASP1707 in healthy elderly men and healthy premenopausal females, and to determine the effect on certain hormones in males. Age and gender is also evaluated.

Part 4 is a randomized, double-blind, placebo-controlled, parallel, multiple dose study to evaluate the safety, tolerability and PK of ASP1707, and its effect on certain hormones in healthy pre-menopausal female subjects.

Panoramica dello studio

Stato

Completato

Condizioni

Intervento / Trattamento

Descrizione dettagliata

Part 1 comprises 7 dose groups of 8 healthy young male subjects. ASP1707 or matching placebo ( 3 to 1 ratio) is given as a single dose under fasted conditions.

The first group receives the lowest dose while the last group receives the highest dose.

Part 2 (Food-Effect) The group consists of 12 healthy young male subjects who receive two separate doses of ASP1707 under fasted or fed conditions. Half of the subjects are dosed first under fasted condition and half of them had first an FDA high-fat breakfast. Subjects receive the alternate treatment on the second occasion. Dosing is separated by at least 7 days or 7 times t1/2 (terminal elimination half-life) as assessed from Part 1.

Part 3 Comprises 4 dose groups of 12 healthy elderly men each, and two groups of 12 healthy premenopausal women. The latter are dosed ASP1707 or placebo in parallel to the 4 male groups. Subjects are fasted or fed depending on observations from Part 2.

Dose levels are defined after evaluating interim safety, tolerability and PK and PD results from Part 1. A lower maximum dose is used in women than in men, based on preclinical data. Dose escalation in the men is independent from dose escalation in the women. Women and men receive once-daily dosing;

Part 4 includes 4 groups, 1 placebo and 3 for ASP1707, each with 9 pre-menopausal women. Subjects in each dose group receive a fixed daily dose. Subjects are domiciled for various intervals during each of 3 menstrual cycles. Dosing occurs for 21 Days during the subjects' second menstrual cycle of the study (Day 1 of Period 2); fasted or fed depending on observations from Part 2.

Tipo di studio

Interventistico

Iscrizione (Effettivo)

176

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

  • Francia
      • Paris, Francia, 75015
        • SGS Life Science Services, Aster

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

18 anni e precedenti (Adulto, Adulto più anziano)

Accetta volontari sani

Sì

Sessi ammissibili allo studio

Tutto

Descrizione

Inclusion Criteria:

Parts 1 & 2:

  • Healthy young male subject aged 18 to 45 years inclusive
  • Body Mass Index more than or equal to 18.5 and less than 30.0 kg/m2.
  • Male subjects must be non-fertile, or must practice an adequate contraceptive method to prevent pregnancies.

Part 3:

  • Healthy elderly male subject aged 55 years or older, or healthy pre-menopausal female subject aged 18 to 45 inclusive.
  • Body Mass Index more than or equal to 18.5 and less than 30.0 kg/m2.
  • Male subject must be non-fertile, or must practice adequate contraceptive methods.
  • Female subjects must be of non-child bearing potential, i.e. surgically sterilized or practice adequate (double barrier) non-hormonal contraceptive methods.

Part 4:

  • Healthy pre-menopausal female subject aged 18 to 45 inclusive.
  • Body Mass Index more than or equal to 18.5 and less than 30.0 kg/m2.
  • Female subjects must be of non-child bearing potential, i.e. surgically sterilized or practice adequate contraceptive methods.
  • Females having a regular menstruation cycle with a duration between 25 up to 30 days.

Exclusion Criteria:

Parts 1 & 2:

  • Male subjects with out-of-range Testosterone levels in serum at screening.
  • Subjects with any history of cancer.
  • Any of the liver function tests (i.e. ALT and AST) above the upper limit of normal.
  • A QTc interval of > 430 ms after repeated measurements.
  • Regular use of any inducer of metabolism (e.g. barbiturates, rifampin) in the 3 months prior to admission to the Clinical Unit.
  • Positive serology test for HBsAg, anti HAV (IgM), anti-HCV or anti-HIV 1+2.

Part 3:

  • Pregnancy within 6 months before screening assessment or breast feeding 3 months before screening.
  • Male subjects with out-of-range T levels in serum at screening.
  • Positive serology test for HBsAg, anti HAV (IgM), anti-HCV or anti-HIV 1+2.

Part 4:

  • Pregnancy within 6 months before screening assessment or breast feeding 3 months before screening.
  • Use of any hormonal interfering contraceptives in the 3 months before admission (for 3 consecutive menstruation cycles) OR any evidence of unovulatory menstrual cycles.
  • Positive serology test for HBsAg, anti HAV (IgM), anti-HCV or anti-HIV 1+2.

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 parallela
  • Mascheramento: Triplicare

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: 1. Single ascending dose (SAD), ASP1707 dose levels 1-7
healthy young male
Droga: ASP1707 single dose of dose levels 1 -7
Oral, dose escalation
Sperimentale: 2. Single ascending dose (SAD), placebo dose levels 1-7
healthy young male
Droga: Placebo single dose of dose levels 1-7
Oral, dose escalation, healthy young male
Sperimentale: 3. Food effect (FE), ASP1707 fasted
Fasted healthy young male
Droga: ASP1707 single dose fasted
Oral, healthy young male
Sperimentale: 4. Food effect (FE), ASP1707 fed
Fed healthy young male
Droga: ASP1707 single dose fed
Oral, healthy young male
Sperimentale: 5. Multiple ascending dose (MAD), ASP1707 dose levels 1-4
healthy elderly male
Droga: ASP1707 multiple dose of dose levels 1-4
Oral, multiple dose escalation, healthy elderly male
Sperimentale: 6. Multiple ascending dose (MAD), Placebo, dose levels 1-4
healthy elderly male
Droga: Placebo multiple dose of dose levels 1-4
Oral, multiple dose escalation, healthy elderly male
Sperimentale: 7. Multiple ascending dose (MAD), ASP1707, dose levels 1-2
healthy pre-menopausal female
Droga: ASP1707 multiple dose of dose levels 1-2
Oral, multiple dose escalation, healthy pre-menopausal female
Sperimentale: 8. Multiple ascending dose (MAD), Placebo dose levels 1-2
healthy pre-menopausal female
Droga: Placebo multiple dose of dose levels 1-2
Oral, multiple dose escalation, healthy pre-menopausal female
Sperimentale: 9. Parallel multiple dose, ASP1707 dose levels 1-3
healthy pre-menopausal female
Droga: ASP1707 parallel multiple dose of dose levels 1-3
Oral, multiple dose, healthy pre-menopausal female
Sperimentale: 10. Parallel multiple dose, Placebo
healthy pre-menopausal female
Droga: Placebo parallel multiple dose
Oral, dose escalation, healthy pre-menopausal female

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Safety assessed by nature, frequency and severity of adverse events
Lasso di tempo: Screening to End of Study Visit (ESV) (up to Day 19 and up to Day 39)
Respectively Part 1 and Part 3
Screening to End of Study Visit (ESV) (up to Day 19 and up to Day 39)
Safety assessed by physical examination
Lasso di tempo: Screening to End of Study Visit (ESV) (up to Day 19 and up to Day 39)
Respectively Part 1 and Part 3
Screening to End of Study Visit (ESV) (up to Day 19 and up to Day 39)
Safety assessed by vital signs
Lasso di tempo: Screening to End of Study Visit (ESV) (up to Day 19 and up to Day 39)
Respectively Part 1 and Part 3. Vital signs include blood pressure and pulse.
Screening to End of Study Visit (ESV) (up to Day 19 and up to Day 39)
Safety assessed by safety laboratory tests
Lasso di tempo: Screening to End of Study Visit (ESV) (up to Day 19 and up to Day 39)
Respectively Part 1 and Part 3, Biochemistry, hematology, and urinalysis
Screening to End of Study Visit (ESV) (up to Day 19 and up to Day 39)
Safety assessed by 12 lead electrocardiogram (ECG)
Lasso di tempo: Screening to End of Study Visit (ESV) (up to Day 19 and up to Day 39)
Respectively Part 1 and Part 3
Screening to End of Study Visit (ESV) (up to Day 19 and up to Day 39)
Safety assessed by continuous cardiac monitoring (Holter)
Lasso di tempo: Days -1 and 21
Part 3
Days -1 and 21
Pharmacokinetics (PK) of ASP1707 measured by area under the plasma concentration - time curve (AUC) extrapolated to time = infinity (AUCinf) in plasma
Lasso di tempo: Pre-dose (Day 1) to Day 5
Part 2
Pre-dose (Day 1) to Day 5
PK of ASP1707 measured by area under the plasma concentration-time curve (AUC) to time from the time of dosing to the last measurable concentration (AUClast) in plasma
Lasso di tempo: Pre-dose (Day 1) to Day 5
Part 2
Pre-dose (Day 1) to Day 5
PK of ASP1707 measured by time to reach quantifiable concentrations (tlag) in plasma
Lasso di tempo: Pre-dose (Day 1) to Day 5
Part 2
Pre-dose (Day 1) to Day 5
PK of ASP1707 measured by time to attain maximum concentration (tmax) in plasma
Lasso di tempo: Pre-dose (Day 1) to Day 5
Part 2
Pre-dose (Day 1) to Day 5
PK of ASP1707 measured by Cmax in plasma
Lasso di tempo: Pre-dose (Day 1) to Day 5
Part 2
Pre-dose (Day 1) to Day 5
PK of ASP1707 measured by terminal elimination half-life (t1/2) in plasma
Lasso di tempo: Pre-dose (Day 1) to Day 5
Part 2
Pre-dose (Day 1) to Day 5
PK of ASP1707 measured by apparent volume of distribution (Vz/F) in plasma
Lasso di tempo: Pre-dose (Day 1) to Day 5
Part 2
Pre-dose (Day 1) to Day 5
PK of ASP1707 measured by apparent clearance (CL/F) in plasma
Lasso di tempo: Pre-dose (Day 1) to Day 5
Part 2
Pre-dose (Day 1) to Day 5
PK of ASP1707 measured by amount excreted unchanged into urine (Ae) from time of dosing until last measurable concentration (Aelast) in urine
Lasso di tempo: Pre-dose (Day 1) to Day 5
Part 2
Pre-dose (Day 1) to Day 5
PK of ASP1707 measured by Ae extrapolated to time = infinity (Aeinf) in urine
Lasso di tempo: Pre-dose (Day 1) to Day 5
Part 2
Pre-dose (Day 1) to Day 5
PK of ASP1707 measured by Ae in % up to the collection time of the last measurable concentration (Aelast%) in urine
Lasso di tempo: Pre-dose (Day 1) to Day 5
Part 2
Pre-dose (Day 1) to Day 5
PK of ASP1707 measured by Ae in % extrapolated to time infinity (Aeinf%) in urine
Lasso di tempo: Pre-dose (Day 1) to Day 5
Part 2
Pre-dose (Day 1) to Day 5
PK of ASP1707 measured by renal clearance (CLR) in urine
Lasso di tempo: Pre-dose (Day 1) to Day 5
Part 2
Pre-dose (Day 1) to Day 5
Pharmacodynamics (PD) of ASP1707 measured by Cmax in plasma
Lasso di tempo: Day -1 to day 15 for period 1, Day 7 to Day 15 for periods 2 and 3
Part 4, period 1, 2 and 3. Estradiol (E2), Follicle-stimulating hormone (FSH) and Luteinizing Hormone (LH) levels
Day -1 to day 15 for period 1, Day 7 to Day 15 for periods 2 and 3
PD of ASP1707 measured by tmax in plasma
Lasso di tempo: Day -1 to day 15 for period 1, Day 7 to Day 15 for periods 2 and 3
Part 4, period 1, 2 and 3. E2, FSH and LH levels
Day -1 to day 15 for period 1, Day 7 to Day 15 for periods 2 and 3
PD of ASP1707 measured by average concentration (Cavg, day 7-15) in plasma
Lasso di tempo: Pre-dose to Day 26
Part 4, period 1, 2 and 3. E2, FSH and LH levels
Pre-dose to Day 26
PD of ASP1707 measured by average concentration (Cavg, day 5-19) in plasma
Lasso di tempo: Pre-dose to Day 26
Part 4, period 3. E2, FSH and LH levels
Pre-dose to Day 26
PD of ASP1707 measured by average concentration (Cavg, day 23-26) in plasma
Lasso di tempo: Pre-dose to Day 26
Part 4, period 2. E2, FSH and LH levels
Pre-dose to Day 26
PD of ASP1707 - maximal duration within therapeutic range
Lasso di tempo: Pre-dose to Day 26
Part 4, period 2. E2 levels
Pre-dose to Day 26
PD of ASP1707 - total duration within therapeutic range (20-50 pg/mL)
Lasso di tempo: Pre-dose to Day 26
Part 4, period 2. E2 levels
Pre-dose to Day 26
PD of ASP1707 - Time of onset therapeutic range
Lasso di tempo: Pre-dose to Day 26
Part 4, period 2. E2 levels
Pre-dose to Day 26
PD of ASP1707 - Time of offset therapeutic range
Lasso di tempo: Pre-dose to Day 26
Part 4, period 2. E2 levels
Pre-dose to Day 26
PD of ASP1707 - Time of start menstruation after last dose of study drug
Lasso di tempo: Pre-dose to Day 26
Part 4, period 3
Pre-dose to Day 26

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
PK profile of ASP1707 in plasma and urine for Part 1
Lasso di tempo: Pre-dose (Day 1) to Day 5
AUCinf, AUClast, tlag, tmax, Cmax, t1/2, Vz/F, CL/F, Aelast, Aeinf, Aelast%, Aeinf%, CLR
Pre-dose (Day 1) to Day 5
Safety profile assessed by nature, frequency and severity of adverse events, physical examination, vital signs, safety laboratory tests and 12 lead ECG
Lasso di tempo: Screening to End of Study Visit (ESV) (Up to 31 days and up to 62 days)
Respectively Part 2 and Part 4
Screening to End of Study Visit (ESV) (Up to 31 days and up to 62 days)
PD profile of ASP1707 for Part 1 and Part 2
Lasso di tempo: Pre-dose (Day 1) to Day 12-19
Testosterone (T), LH and FSH levels: Cmin, tmin, maximal %Reduction and T only: Number and percentage of subjects with T castration level (= T < 0.5 ng/mL) after single dose, Time of onset of T < 0.5 ng/mL after single dose, Duration of T <0.5 ng/mL after single dose
Pre-dose (Day 1) to Day 12-19
PD profile of ASP1707 for Part 3
Lasso di tempo: Pre-dose (Day 1) to Day 39
T, LH and FSH levels: Cmin, tmin, maximal %Reduction T only: Number and percentage of subjects with T < 0.5 ng/mL at any time post-first dose, Number and percentage of subjects with T < 0.5 ng/mL after last dose, Number of subjects reaching T<0.5 ng/mL for ≥14 days, Day of onset of T < 0.5 ng/mL after multiple doses of ASP1707 (T < 0.5 ng/mL for the first time), Time of onset of T < 0.5 ng/mL after first dose, Duration of T < 0.5 ng/mL after single dose and during multiple dosing, Total duration, Maximal duration:Time from last dose to return to baseline levels for T, LH and FSH, Duration of T < 0.5 ng/mL after last dose
Pre-dose (Day 1) to Day 39
PK profile of ASP1707 in plasma and urine for Part 3
Lasso di tempo: Pre-dose (Day 1) to Day 25
AUCinf, AUClast, tlag, tmax, Cmax, t1/2, Vz/F, CL/F, Aelast, Aeinf, Aelast%, Aeinf%, CLR, Ctrough, AUC during the time interval between consecutive dosing (AUCtau), Accumulation Ratio (Rac), Peak Trough Ratio (PTR), Ae during the time interval between consecutive dosing (Aetau), Aetau as percentage of total dose (Aetau%), Ae during the time interval between consecutive dosing (AUCtau), (AUC0-24h), Ae0-24h, Ae0-24h%
Pre-dose (Day 1) to Day 25
PK profile of ASP1707 in plasma and urine for Part 4
Lasso di tempo: Pre-dose (Day 23) to Day 25
AUCtau, tmax, Cmax, t1/2, Vz/F, CL/F, CLR, Ctrough, PTR, Aetau, Aetau%,
Pre-dose (Day 23) to Day 25

Collaboratori e investigatori

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

Sponsor

Astellas Pharma Europe B.V.

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

1 giugno 2010

Completamento primario (Effettivo)

1 agosto 2011

Completamento dello studio (Effettivo)

1 agosto 2011

Date di iscrizione allo studio

Primo inviato

14 novembre 2014

Primo inviato che soddisfa i criteri di controllo qualità

17 febbraio 2015

Primo Inserito (Stima)

23 febbraio 2015

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Stima)

23 febbraio 2015

Ultimo aggiornamento inviato che soddisfa i criteri QC

17 febbraio 2015

Ultimo verificato

1 febbraio 2015

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Altri numeri di identificazione dello studio

  • 1707-CL-0001
  • 2010-018292-21 (Numero EudraCT)

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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