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 de fevereiro de 2015 atualizado por: 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.
Visão geral do estudo
Status
Concluído
Intervenção / Tratamento
- Medicamento: ASP1707 single dose of dose levels 1 -7
- Medicamento: Placebo single dose of dose levels 1-7
- Medicamento: ASP1707 single dose fasted
- Medicamento: ASP1707 single dose fed
- Medicamento: ASP1707 multiple dose of dose levels 1-4
- Medicamento: Placebo multiple dose of dose levels 1-4
- Medicamento: ASP1707 multiple dose of dose levels 1-2
- Medicamento: Placebo multiple dose of dose levels 1-2
- Medicamento: ASP1707 parallel multiple dose of dose levels 1-3
- Medicamento: Placebo parallel multiple dose
Descrição detalhada
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 de estudo
Intervencional
Inscrição (Real)
176
Estágio
- Fase 1
Contactos e Locais
Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.
Locais de estudo
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Paris, França, 75015
- SGS Life Science Services, Aster
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Critérios de participação
Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.
Critérios de elegibilidade
Idades elegíveis para estudo
18 anos e mais velhos (Adulto, Adulto mais velho)
Aceita Voluntários Saudáveis
Sim
Gêneros Elegíveis para o Estudo
Tudo
Descrição
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.
Plano de estudo
Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Ciência básica
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Triplo
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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Experimental: 1. Single ascending dose (SAD), ASP1707 dose levels 1-7
healthy young male
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Oral, dose escalation
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Experimental: 2. Single ascending dose (SAD), placebo dose levels 1-7
healthy young male
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Oral, dose escalation, healthy young male
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Experimental: 3. Food effect (FE), ASP1707 fasted
Fasted healthy young male
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Oral, healthy young male
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Experimental: 4. Food effect (FE), ASP1707 fed
Fed healthy young male
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Oral, healthy young male
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Experimental: 5. Multiple ascending dose (MAD), ASP1707 dose levels 1-4
healthy elderly male
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Oral, multiple dose escalation, healthy elderly male
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Experimental: 6. Multiple ascending dose (MAD), Placebo, dose levels 1-4
healthy elderly male
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Oral, multiple dose escalation, healthy elderly male
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Experimental: 7. Multiple ascending dose (MAD), ASP1707, dose levels 1-2
healthy pre-menopausal female
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Oral, multiple dose escalation, healthy pre-menopausal female
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Experimental: 8. Multiple ascending dose (MAD), Placebo dose levels 1-2
healthy pre-menopausal female
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Oral, multiple dose escalation, healthy pre-menopausal female
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Experimental: 9. Parallel multiple dose, ASP1707 dose levels 1-3
healthy pre-menopausal female
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Oral, multiple dose, healthy pre-menopausal female
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Experimental: 10. Parallel multiple dose, Placebo
healthy pre-menopausal female
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Oral, dose escalation, healthy pre-menopausal female
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Safety assessed by nature, frequency and severity of adverse events
Prazo: Screening to End of Study Visit (ESV) (up to Day 19 and up to Day 39)
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Respectively Part 1 and Part 3
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Screening to End of Study Visit (ESV) (up to Day 19 and up to Day 39)
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Safety assessed by physical examination
Prazo: 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)
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Safety assessed by vital signs
Prazo: Screening to End of Study Visit (ESV) (up to Day 19 and up to Day 39)
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Respectively Part 1 and Part 3. Vital signs include blood pressure and pulse.
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Screening to End of Study Visit (ESV) (up to Day 19 and up to Day 39)
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Safety assessed by safety laboratory tests
Prazo: Screening to End of Study Visit (ESV) (up to Day 19 and up to Day 39)
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Respectively Part 1 and Part 3, Biochemistry, hematology, and urinalysis
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Screening to End of Study Visit (ESV) (up to Day 19 and up to Day 39)
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Safety assessed by 12 lead electrocardiogram (ECG)
Prazo: Screening to End of Study Visit (ESV) (up to Day 19 and up to Day 39)
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Respectively Part 1 and Part 3
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Screening to End of Study Visit (ESV) (up to Day 19 and up to Day 39)
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Safety assessed by continuous cardiac monitoring (Holter)
Prazo: Days -1 and 21
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Part 3
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Days -1 and 21
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Pharmacokinetics (PK) of ASP1707 measured by area under the plasma concentration - time curve (AUC) extrapolated to time = infinity (AUCinf) in plasma
Prazo: Pre-dose (Day 1) to Day 5
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Part 2
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Pre-dose (Day 1) to Day 5
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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
Prazo: Pre-dose (Day 1) to Day 5
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Part 2
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Pre-dose (Day 1) to Day 5
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PK of ASP1707 measured by time to reach quantifiable concentrations (tlag) in plasma
Prazo: Pre-dose (Day 1) to Day 5
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Part 2
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Pre-dose (Day 1) to Day 5
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PK of ASP1707 measured by time to attain maximum concentration (tmax) in plasma
Prazo: Pre-dose (Day 1) to Day 5
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Part 2
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Pre-dose (Day 1) to Day 5
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PK of ASP1707 measured by Cmax in plasma
Prazo: Pre-dose (Day 1) to Day 5
|
Part 2
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Pre-dose (Day 1) to Day 5
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PK of ASP1707 measured by terminal elimination half-life (t1/2) in plasma
Prazo: Pre-dose (Day 1) to Day 5
|
Part 2
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Pre-dose (Day 1) to Day 5
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PK of ASP1707 measured by apparent volume of distribution (Vz/F) in plasma
Prazo: Pre-dose (Day 1) to Day 5
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Part 2
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Pre-dose (Day 1) to Day 5
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PK of ASP1707 measured by apparent clearance (CL/F) in plasma
Prazo: Pre-dose (Day 1) to Day 5
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Part 2
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Pre-dose (Day 1) to Day 5
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PK of ASP1707 measured by amount excreted unchanged into urine (Ae) from time of dosing until last measurable concentration (Aelast) in urine
Prazo: Pre-dose (Day 1) to Day 5
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Part 2
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Pre-dose (Day 1) to Day 5
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PK of ASP1707 measured by Ae extrapolated to time = infinity (Aeinf) in urine
Prazo: Pre-dose (Day 1) to Day 5
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Part 2
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Pre-dose (Day 1) to Day 5
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PK of ASP1707 measured by Ae in % up to the collection time of the last measurable concentration (Aelast%) in urine
Prazo: Pre-dose (Day 1) to Day 5
|
Part 2
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Pre-dose (Day 1) to Day 5
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PK of ASP1707 measured by Ae in % extrapolated to time infinity (Aeinf%) in urine
Prazo: Pre-dose (Day 1) to Day 5
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Part 2
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Pre-dose (Day 1) to Day 5
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PK of ASP1707 measured by renal clearance (CLR) in urine
Prazo: Pre-dose (Day 1) to Day 5
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Part 2
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Pre-dose (Day 1) to Day 5
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Pharmacodynamics (PD) of ASP1707 measured by Cmax in plasma
Prazo: Day -1 to day 15 for period 1, Day 7 to Day 15 for periods 2 and 3
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Part 4, period 1, 2 and 3. Estradiol (E2), Follicle-stimulating hormone (FSH) and Luteinizing Hormone (LH) levels
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Day -1 to day 15 for period 1, Day 7 to Day 15 for periods 2 and 3
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PD of ASP1707 measured by tmax in plasma
Prazo: Day -1 to day 15 for period 1, Day 7 to Day 15 for periods 2 and 3
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Part 4, period 1, 2 and 3. E2, FSH and LH levels
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Day -1 to day 15 for period 1, Day 7 to Day 15 for periods 2 and 3
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PD of ASP1707 measured by average concentration (Cavg, day 7-15) in plasma
Prazo: Pre-dose to Day 26
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Part 4, period 1, 2 and 3. E2, FSH and LH levels
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Pre-dose to Day 26
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PD of ASP1707 measured by average concentration (Cavg, day 5-19) in plasma
Prazo: Pre-dose to Day 26
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Part 4, period 3. E2, FSH and LH levels
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Pre-dose to Day 26
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PD of ASP1707 measured by average concentration (Cavg, day 23-26) in plasma
Prazo: Pre-dose to Day 26
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Part 4, period 2. E2, FSH and LH levels
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Pre-dose to Day 26
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PD of ASP1707 - maximal duration within therapeutic range
Prazo: Pre-dose to Day 26
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Part 4, period 2. E2 levels
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Pre-dose to Day 26
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PD of ASP1707 - total duration within therapeutic range (20-50 pg/mL)
Prazo: Pre-dose to Day 26
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Part 4, period 2. E2 levels
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Pre-dose to Day 26
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PD of ASP1707 - Time of onset therapeutic range
Prazo: Pre-dose to Day 26
|
Part 4, period 2. E2 levels
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Pre-dose to Day 26
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PD of ASP1707 - Time of offset therapeutic range
Prazo: Pre-dose to Day 26
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Part 4, period 2. E2 levels
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Pre-dose to Day 26
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PD of ASP1707 - Time of start menstruation after last dose of study drug
Prazo: Pre-dose to Day 26
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Part 4, period 3
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Pre-dose to Day 26
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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PK profile of ASP1707 in plasma and urine for Part 1
Prazo: Pre-dose (Day 1) to Day 5
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AUCinf, AUClast, tlag, tmax, Cmax, t1/2, Vz/F, CL/F, Aelast, Aeinf, Aelast%, Aeinf%, CLR
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Pre-dose (Day 1) to Day 5
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Safety profile assessed by nature, frequency and severity of adverse events, physical examination, vital signs, safety laboratory tests and 12 lead ECG
Prazo: Screening to End of Study Visit (ESV) (Up to 31 days and up to 62 days)
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Respectively Part 2 and Part 4
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Screening to End of Study Visit (ESV) (Up to 31 days and up to 62 days)
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PD profile of ASP1707 for Part 1 and Part 2
Prazo: Pre-dose (Day 1) to Day 12-19
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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
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Pre-dose (Day 1) to Day 12-19
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PD profile of ASP1707 for Part 3
Prazo: Pre-dose (Day 1) to Day 39
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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
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Pre-dose (Day 1) to Day 39
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PK profile of ASP1707 in plasma and urine for Part 3
Prazo: Pre-dose (Day 1) to Day 25
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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%
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Pre-dose (Day 1) to Day 25
|
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PK profile of ASP1707 in plasma and urine for Part 4
Prazo: Pre-dose (Day 23) to Day 25
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AUCtau, tmax, Cmax, t1/2, Vz/F, CL/F, CLR, Ctrough, PTR, Aetau, Aetau%,
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Pre-dose (Day 23) to Day 25
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Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Datas de registro do estudo
Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.
Datas Principais do Estudo
Início do estudo
1 de junho de 2010
Conclusão Primária (Real)
1 de agosto de 2011
Conclusão do estudo (Real)
1 de agosto de 2011
Datas de inscrição no estudo
Enviado pela primeira vez
14 de novembro de 2014
Enviado pela primeira vez que atendeu aos critérios de CQ
17 de fevereiro de 2015
Primeira postagem (Estimativa)
23 de fevereiro de 2015
Atualizações de registro de estudo
Última Atualização Postada (Estimativa)
23 de fevereiro de 2015
Última atualização enviada que atendeu aos critérios de controle de qualidade
17 de fevereiro de 2015
Última verificação
1 de fevereiro de 2015
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Outros números de identificação do estudo
- 1707-CL-0001
- 2010-018292-21 (Número EudraCT)
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