Tämä sivu käännettiin automaattisesti, eikä käännösten tarkkuutta voida taata. Katso englanninkielinen versio lähdetekstiä varten.

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

tiistai 17. helmikuuta 2015 päivittänyt: 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.

Tutkimuksen yleiskatsaus

Tila

Valmis

Ehdot

Interventio / Hoito

Yksityiskohtainen kuvaus

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.

Opintotyyppi

Interventio

Ilmoittautuminen (Todellinen)

176

Vaihe

  • Vaihe 1

Yhteystiedot ja paikat

Tässä osiossa on tutkimuksen suorittajien yhteystiedot ja tiedot siitä, missä tämä tutkimus suoritetaan.

Opiskelupaikat

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

Osallistumiskriteerit

Tutkijat etsivät ihmisiä, jotka sopivat tiettyyn kuvaukseen, jota kutsutaan kelpoisuuskriteereiksi. Joitakin esimerkkejä näistä kriteereistä ovat henkilön yleinen terveydentila tai aiemmat hoidot.

Kelpoisuusvaatimukset

Opintokelpoiset iät

18 vuotta ja vanhemmat (Aikuinen, Vanhempi Aikuinen)

Hyväksyy terveitä vapaaehtoisia

Joo

Sukupuolet, jotka voivat opiskella

Kaikki

Kuvaus

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.

Opintosuunnitelma

Tässä osiossa on tietoja tutkimussuunnitelmasta, mukaan lukien kuinka tutkimus on suunniteltu ja mitä tutkimuksella mitataan.

Miten tutkimus on suunniteltu?

Suunnittelun yksityiskohdat

  • Ensisijainen käyttötarkoitus: Perustiede
  • Jako: Satunnaistettu
  • Inventiomalli: Rinnakkaistehtävä
  • Naamiointi: Kolminkertaistaa

Aseet ja interventiot

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

Mitä tutkimuksessa mitataan?

Ensisijaiset tulostoimenpiteet

Tulosmittaus
Toimenpiteen kuvaus
Aikaikkuna
Safety assessed by nature, frequency and severity of adverse events
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: Pre-dose (Day 1) to Day 5
Part 2
Pre-dose (Day 1) to Day 5
PK of ASP1707 measured by Cmax in plasma
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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)
Aikaikkuna: Pre-dose to Day 26
Part 4, period 2. E2 levels
Pre-dose to Day 26
PD of ASP1707 - Time of onset therapeutic range
Aikaikkuna: Pre-dose to Day 26
Part 4, period 2. E2 levels
Pre-dose to Day 26
PD of ASP1707 - Time of offset therapeutic range
Aikaikkuna: 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
Aikaikkuna: Pre-dose to Day 26
Part 4, period 3
Pre-dose to Day 26

Toissijaiset tulostoimenpiteet

Tulosmittaus
Toimenpiteen kuvaus
Aikaikkuna
PK profile of ASP1707 in plasma and urine for Part 1
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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

Yhteistyökumppanit ja tutkijat

Täältä löydät tähän tutkimukseen osallistuvat ihmiset ja organisaatiot.

Sponsori

Astellas Pharma Europe B.V.

Opintojen ennätyspäivät

Nämä päivämäärät seuraavat ClinicalTrials.gov-sivustolle lähetettyjen tutkimustietueiden ja yhteenvetojen edistymistä. National Library of Medicine (NLM) tarkistaa tutkimustiedot ja raportoidut tulokset varmistaakseen, että ne täyttävät tietyt laadunvalvontastandardit, ennen kuin ne julkaistaan ​​julkisella verkkosivustolla.

Opi tärkeimmät päivämäärät

Opiskelun aloitus

Tiistai 1. kesäkuuta 2010

Ensisijainen valmistuminen (Todellinen)

Maanantai 1. elokuuta 2011

Opintojen valmistuminen (Todellinen)

Maanantai 1. elokuuta 2011

Opintoihin ilmoittautumispäivät

Ensimmäinen lähetetty

Perjantai 14. marraskuuta 2014

Ensimmäinen toimitettu, joka täytti QC-kriteerit

Tiistai 17. helmikuuta 2015

Ensimmäinen Lähetetty (Arvio)

Maanantai 23. helmikuuta 2015

Tutkimustietojen päivitykset

Viimeisin päivitys julkaistu (Arvio)

Maanantai 23. helmikuuta 2015

Viimeisin lähetetty päivitys, joka täytti QC-kriteerit

Tiistai 17. helmikuuta 2015

Viimeksi vahvistettu

Sunnuntai 1. helmikuuta 2015

Lisää tietoa

Tähän tutkimukseen liittyvät termit

Avainsanat

Muut tutkimustunnusnumerot

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

Nämä tiedot haettiin suoraan verkkosivustolta clinicaltrials.gov ilman muutoksia. Jos sinulla on pyyntöjä muuttaa, poistaa tai päivittää tutkimustietojasi, ota yhteyttä register@clinicaltrials.gov. Heti kun muutos on otettu käyttöön osoitteessa clinicaltrials.gov, se päivitetään automaattisesti myös verkkosivustollemme .

Tilaa