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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 februari 2015 bijgewerkt door: 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.

Studie Overzicht

Toestand

Voltooid

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

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.

Studietype

Ingrijpend

Inschrijving (Werkelijk)

176

Fase

  • Fase 1

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

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

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar en ouder (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Ja

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

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.

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Fundamentele wetenschap
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Verdrievoudigen

Wapens en interventies

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

Wat meet het onderzoek?

Primaire uitkomstmaten

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

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
PK profile of ASP1707 in plasma and urine for Part 1
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Astellas Pharma Europe B.V.

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

1 juni 2010

Primaire voltooiing (Werkelijk)

1 augustus 2011

Studie voltooiing (Werkelijk)

1 augustus 2011

Studieregistratiedata

Eerst ingediend

14 november 2014

Eerst ingediend dat voldeed aan de QC-criteria

17 februari 2015

Eerst geplaatst (Schatting)

23 februari 2015

Updates van studierecords

Laatste update geplaatst (Schatting)

23 februari 2015

Laatste update ingediend die voldeed aan QC-criteria

17 februari 2015

Laatst geverifieerd

1 februari 2015

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Andere studie-ID-nummers

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

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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