Pharmacokinetics of ASP8477Phase 1NCT02220777
A Study to Assess the Effects of Single Ascending Doses (SAD) of ASP8477, the Effect That Food Has on the Drug, and the Interaction Between ASP8477 and Omeprazole in Healthy Postmenopausal Females and Healthy Young Vasectomized Males
A Phase 1 study testing ASP8477 and omeprazole in people with Pharmacokinetics of ASP8477 and Pharmacodynamics of ASP8477, run by Astellas Pharma Europe B.V. at 2 sites in 2 countries.
Trial summary
This is a 4-part study. Part I assesses the safety and tolerability of single ascending doses of ASP8477 or a placebo under fasted conditions in postmenopausal subjects. Part II is similar to part I except that the study is conducted in young, vasectomized males. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Pharmacokinetics of ASP8477, Pharmacodynamics of ASP8477
- What is being tested?
- ASP8477 and omeprazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 72 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Nov 2010to May 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy young (<65 years of age at first planned dose) postmenopausal female (Parts I, III, and IV).
- Healthy young vasectomized male subject aged 18-55 years inclusive (Part II).
- Body Mass index between 18.5 and 30.0 kg/m2 inclusive.
Who cannot join
- Known or suspected hypersensitivity to ASP8477 or any of the components of the formulations used.
- Any of the liver function tests above the upper limit of normal.
- A family history of psychiatric disorders.
- Use of grapefruit (more than 3 x 200 ml) or marmalade (more than three times) in the week prior to admission to the Clinical Unit, as reported by the subject.
- Use of xanthine-containing beverages within 48 hours before admission.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: A Double-blind, Randomized, Placebo-controlled Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Ascending Oral Doses of ASP8477 in Healthy Postmenopausal Females and Healthy Young Vasectomized Males, Including a Food Effect Part and a Part to Investigate the Interaction Between ASP8477 and Omeprazole
This is a 4-part study. Part I assesses the safety and tolerability of single ascending doses of ASP8477 or a placebo under fasted conditions in postmenopausal subjects. Part II is similar to part I except that the study is conducted in young, vasectomized males.
Part III assesses the effect of food (fed or fasted conditions) on ASP8477 in postmenopausal subjects.
Part IV assesses the drug-drug interaction between ASP8477 and omeprazole in postmenopausal subjects.
Read the detailed description
Part I (SAD) in healthy postmenopausal females evaluates the safety, and tolerability, and defines Maximum Tolerated Dose = MTD, pharmacokinetics, and pharmacodynamics of single ascending oral doses (SAD) of ASP8477. It is anticipated that around 7 doses are required to cover the range from the safe starting dose until the MTD. Study medication is administered under fasted conditions. Based on the safety, PK, and clinical observation of the subjects, the dose escalation scheme may be adapted. Escalation to the next dose only proceeds after review of the safety, tolerability, and PK from the previous treatment period.
Part II (SAD in young, healthy, vasectomized males) is similar to Part I, one cohort of 12 subjects are treated with two doses of ASP8477 plus placebo. The doses tested depend on the safety data and pharmacodynamic profiles obtained in Part I, but is not expected to exceed MTD. The rationale for this part is to bridge the data obtained in female subjects to male subjects.
Part III (food effect) postmenopausal females receive ASP8477 once under fasted and once under fed conditions in two separate periods in random order. The dose does not exceed 1/3 of the MTD or, if that has not been reached, 1/3 of the highest tested dose in Part I. Subjects stay in the clinic for 2 periods of 5 to 7 days (depending on the terminal half life, resulting from Part I). Subjects are admitted on Day -2 per treatment period. Subjects' feeding status is the same as on Day 1 of the same treatment period. Subjects are given a single dose of ASP8477 under fed or fasting conditions on Day 1. After final discharge, subjects return for an End of Study Visit (ESV) 5-9 days later.
Part IV (ASP8477-omeprazole drug-drug interaction) postmenopausal subjects are randomized to receive omeprazole once alone and once with ASP8477 in two separate periods (in random order). The dose of ASP8477 is the MTD or, if that is not been reached, the highest tested dose in Part I. Omeprazole is chosen as target drug as it is a model substrate for CYP2C19 (accepted by FDA) and ASP8477 is known to have the strongest inhibitory effect on CYP2C19. Subjects are admitted on Day -1 and stay for 2 periods of 4 days. Subjects are given a single dose of omeprazole alone or with ASP8477 (in randomized order) on Day 1. Study medication is administered under fasted conditions. Subjects are discharged on Day 3 and return for an ESV 5-9 days later.
- Being tested
- ASP8477, omeprazole, Placebo
- Keywords
- MTD (Maximum Tolerated Dose), Food effect, Postmenopausal subjects, Vasectomized subjects, FIH (First In Humans), SAD (Single Ascending Dose), DDI (Drug-Drug Interaction)
- Medical subject headings
- Metatropic dwarfism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ASP8477Drug
oral
omeprazoleDrug
oral
PlaceboDrug
oral
| Study group | Role | What they receive |
|---|---|---|
| 1. ASP8477 and placebo | Experimental | Part 1: SAD in postmenopausal females and Part 2: SAD in vasectomized male Receives: Drug: ASP8477; Drug: Placebo |
| 2. ASP8477 alone | Experimental | Part 3, fasted or fed Receives: Drug: ASP8477 |
| 3. omeprazole alone | Experimental | Part 4, Drug-Drug Interaction Receives: Drug: omeprazole |
| 4. ASP8477 + omeprazole | Experimental | Part 4: Drug-Drug Interaction Receives: Drug: ASP8477; Drug: omeprazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety as assessed by recording adverse events, physical examination, laboratory assessments, vital signs, electrocardiograms (ECGs), cortisol levels, arterial carbon dioxide and oxygen saturation
For Part I and II Bond-Lader Visual Analogue Scale (VAS) and Bowdle VAS assessments will also be taken.
Measured: Day1 to End of Study Visit (5-9 days after final discharge)
The assessment of pharmacokinetic parameter of ASP8477 measured by Maximum concentration (Cmax), in plasma
Maximum concentration (Cmax)
Measured: Day 1 to Day 3
The assessment of pharmacokinetic parameter of ASP8477 measured by Time to attain Cmax (tmax) in plasma
Time to attain Cmax (tmax)
Measured: Day 1 to Day 3
The assessment of pharmacokinetic parameter of ASP8477 measured by Area Under the Curve (AUC) extrapolated until infinity (AUCinf) in plasma
Area Under the Curve (AUC) extrapolated until infinity (AUCinf)
Measured: Day 1 to Day 3
The assessment of pharmacokinetic parameter of ASP8477 measured by AUC until last sample taken (AUClast) in plasma
AUC until last sample taken (AUClast), Absorption lag time (tlag), Apparent terminal elimination half-life (t1/2), Apparent volume of distribution (Vz/F), Apparent total body plasma clearance (CL/F)
Measured: Day 1 to Day 3
The assessment of pharmacokinetic parameter of ASP8477 measured by Absorption lag time (tlag) in plasma
Absorption lag time (tlag)
Measured: Day 1 to Day 3
The assessment of pharmacokinetic parameter of ASP8477 measured by Apparent terminal elimination half-life (t1/2) in plasma
Apparent terminal elimination half-life (t1/2)
Measured: Day 1 to Day 3
The assessment of pharmacokinetic parameter of ASP8477 measured by Apparent volume of distribution (Vz/F) in plasma
Apparent volume of distribution (Vz/F)
Measured: Day 1 to Day 3
The assessment of pharmacokinetic parameter of ASP8477 measured by Apparent total body plasma clearance (CL/F) in plasma
Apparent total body plasma clearance (CL/F)
Measured: Day 1 to Day 3
The assessment of pharmacokinetic parameter of ASP8477 measured by Amount excreted in urine until last sample (Aelast) in urine
Amount excreted in urine until last sample (Aelast)
Measured: Day 1 to Day 3
The assessment of pharmacokinetic parameter of ASP8477 measured by Cumulative amount of unchanged drug excreted into the urine from time zero to infinity after single dose (Aeinf) in urine
Cumulative amount of unchanged drug excreted into the urine from time zero to infinity after single dose (Aeinf)
Measured: Day 1 to Day 3
The assessment of pharmacokinetic parameter of ASP8477 measured by Percentage of unchanged drug excreted into the urine from time of last measurable concentration (Aelast%) in urine
Percentage of unchanged drug excreted into the urine from time of last measurable concentration (Aelast%)
Measured: Day 1 to Day 3
The assessment of pharmacokinetic parameter of ASP8477 measured by Percentage of unchanged drug excreted into the urine from time zero to infinity after single dose (Aeinf%) in urine
Percentage of unchanged drug excreted into the urine from time zero to infinity after single dose (Aeinf%)
Measured: Day 1 to Day 3
The assessment of pharmacokinetic parameter of ASP8477 measured by Renal clearance (CLR) in urine
Renal clearance (CLR)
Measured: Day 1 to Day 3
Secondary outcomes (2)
The assessment of pharmacokinetics of omeprazole measured by plasma concentration
Cmax, tmax, AUCinf, AUClast, t1/2, Vz/F, CL/F
Measured: Day 1 to Day 3
The assessment of pharmacodynamics of ASP8477 measured by serum concentration
serum concentration of endogenous substrates, volume of urine production, GFR and intra-ocular pressure
Measured: Day 1 to Day 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2014 (estimated)
- Study startNov 2010
- Primary completionMay 2011
- Study completionMay 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pharmacokinetics of ASP8477Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- Astellas Pharma Europe B.V.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Manager, Study chair, Astellas Pharma Europe B.V.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02220777
- Sponsor's protocol ID
- 8477-CL-0001
- Other IDs
- 2009-017865-42, 2009
- Status last verified
- Aug 2014
- First submitted
- 18 Aug 2014
- Last updated
- 20 Aug 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blind, Randomized, Placebo-controlled Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Ascending Oral Doses of ASP8477 in Healthy Postmenopausal Females and Healthy Young Vasectomized Males, Including a Food Effect Part and a Part to Investigate the Interaction Between ASP8477 and Omeprazole
- ClinicalTrials.gov ID
- NCT02220777
- Acronym / sponsor ID
- 8477-CL-0001
- Keywords
- MTD (Maximum Tolerated Dose), Food effect, Postmenopausal subjects, Vasectomized subjects, FIH (First In Humans), SAD (Single Ascending Dose), DDI (Drug-Drug Interaction)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- Astellas Pharma Europe B.V.Industry (pharma, biotech, devices)
- Study start
- Nov 2010
- Primary completion
- May 2011 (actual)
- Study completion
- May 2011 (actual)
- First posted
- 20 Aug 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a 4-part study. Part I assesses the safety and tolerability of single ascending doses of ASP8477 or a placebo under fasted conditions in postmenopausal subjects. Part II is similar to part I except that the study is conducted in young, vasectomized males.
Part III assesses the effect of food (fed or fasted conditions) on ASP8477 in postmenopausal subjects.
Part IV assesses the drug-drug interaction between ASP8477 and omeprazole in postmenopausal subjects.
Detailed description
Part I (SAD) in healthy postmenopausal females evaluates the safety, and tolerability, and defines Maximum Tolerated Dose = MTD, pharmacokinetics, and pharmacodynamics of single ascending oral doses (SAD) of ASP8477. It is anticipated that around 7 doses are required to cover the range from the safe starting dose until the MTD. Study medication is administered under fasted conditions. Based on the safety, PK, and clinical observation of the subjects, the dose escalation scheme may be adapted. Escalation to the next dose only proceeds after review of the safety, tolerability, and PK from the previous treatment period.
Part II (SAD in young, healthy, vasectomized males) is similar to Part I, one cohort of 12 subjects are treated with two doses of ASP8477 plus placebo. The doses tested depend on the safety data and pharmacodynamic profiles obtained in Part I, but is not expected to exceed MTD. The rationale for this part is to bridge the data obtained in female subjects to male subjects.
Part III (food effect) postmenopausal females receive ASP8477 once under fasted and once under fed conditions in two separate periods in random order. The dose does not exceed 1/3 of the MTD or, if that has not been reached, 1/3 of the highest tested dose in Part I. Subjects stay in the clinic for 2 periods of 5 to 7 days (depending on the terminal half life, resulting from Part I). Subjects are admitted on Day -2 per treatment period. Subjects' feeding status is the same as on Day 1 of the same treatment period. Subjects are given a single dose of ASP8477 under fed or fasting conditions on Day 1. After final discharge, subjects return for an End of Study Visit (ESV) 5-9 days later.
Part IV (ASP8477-omeprazole drug-drug interaction) postmenopausal subjects are randomized to receive omeprazole once alone and once with ASP8477 in two separate periods (in random order). The dose of ASP8477 is the MTD or, if that is not been reached, the highest tested dose in Part I. Omeprazole is chosen as target drug as it is a model substrate for CYP2C19 (accepted by FDA) and ASP8477 is known to have the strongest inhibitory effect on CYP2C19. Subjects are admitted on Day -1 and stay for 2 periods of 4 days. Subjects are given a single dose of omeprazole alone or with ASP8477 (in randomized order) on Day 1. Study medication is administered under fasted conditions. Subjects are discharged on Day 3 and return for an ESV 5-9 days later.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1. ASP8477 and placebo | Experimental | Drug: ASP8477, Drug: PlaceboPart 1: SAD in postmenopausal females and Part 2: SAD in vasectomized male |
| 2. ASP8477 alone | Experimental | Drug: ASP8477Part 3, fasted or fed |
| 3. omeprazole alone | Experimental | Drug: omeprazolePart 4, Drug-Drug Interaction |
| 4. ASP8477 + omeprazole | Experimental | Drug: ASP8477, Drug: omeprazolePart 4: Drug-Drug Interaction |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Healthy young (<65 years of age at first planned dose) postmenopausal female (Parts I, III, and IV).
- Healthy young vasectomized male subject aged 18-55 years inclusive (Part II).
- Body Mass index between 18.5 and 30.0 kg/m2 inclusive.
Key exclusion criteria (5 listed)
- Known or suspected hypersensitivity to ASP8477 or any of the components of the formulations used.
- Any of the liver function tests above the upper limit of normal.
- A family history of psychiatric disorders.
- Use of grapefruit (more than 3 x 200 ml) or marmalade (more than three times) in the week prior to admission to the Clinical Unit, as reported by the subject.
- Use of xanthine-containing beverages within 48 hours before admission.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ASP8477oral | Drug | 1. ASP8477 and placebo, 2. ASP8477 alone, 4. ASP8477 + omeprazole |
| omeprazoleoral | Drug | 3. omeprazole alone, 4. ASP8477 + omeprazole |
| Placebooral | Drug | 1. ASP8477 and placebo |
Primary outcome
Safety as assessed by recording adverse events, physical examination, laboratory assessments, vital signs, electrocardiograms (ECGs), cortisol levels, arterial carbon dioxide and oxygen saturation
Time frame: Day1 to End of Study Visit (5-9 days after final discharge)
For Part I and II Bond-Lader Visual Analogue Scale (VAS) and Bowdle VAS assessments will also be taken.
The assessment of pharmacokinetic parameter of ASP8477 measured by Maximum concentration (Cmax), in plasma
Time frame: Day 1 to Day 3
Maximum concentration (Cmax)
The assessment of pharmacokinetic parameter of ASP8477 measured by Time to attain Cmax (tmax) in plasma
Time frame: Day 1 to Day 3
Time to attain Cmax (tmax)
The assessment of pharmacokinetic parameter of ASP8477 measured by Area Under the Curve (AUC) extrapolated until infinity (AUCinf) in plasma
Time frame: Day 1 to Day 3
Area Under the Curve (AUC) extrapolated until infinity (AUCinf)
The assessment of pharmacokinetic parameter of ASP8477 measured by AUC until last sample taken (AUClast) in plasma
Time frame: Day 1 to Day 3
AUC until last sample taken (AUClast), Absorption lag time (tlag), Apparent terminal elimination half-life (t1/2), Apparent volume of distribution (Vz/F), Apparent total body plasma clearance (CL/F)
The assessment of pharmacokinetic parameter of ASP8477 measured by Absorption lag time (tlag) in plasma
Time frame: Day 1 to Day 3
Absorption lag time (tlag)
The assessment of pharmacokinetic parameter of ASP8477 measured by Apparent terminal elimination half-life (t1/2) in plasma
Time frame: Day 1 to Day 3
Apparent terminal elimination half-life (t1/2)
The assessment of pharmacokinetic parameter of ASP8477 measured by Apparent volume of distribution (Vz/F) in plasma
Time frame: Day 1 to Day 3
Apparent volume of distribution (Vz/F)
The assessment of pharmacokinetic parameter of ASP8477 measured by Apparent total body plasma clearance (CL/F) in plasma
Time frame: Day 1 to Day 3
Apparent total body plasma clearance (CL/F)
The assessment of pharmacokinetic parameter of ASP8477 measured by Amount excreted in urine until last sample (Aelast) in urine
Time frame: Day 1 to Day 3
Amount excreted in urine until last sample (Aelast)
The assessment of pharmacokinetic parameter of ASP8477 measured by Cumulative amount of unchanged drug excreted into the urine from time zero to infinity after single dose (Aeinf) in urine
Time frame: Day 1 to Day 3
Cumulative amount of unchanged drug excreted into the urine from time zero to infinity after single dose (Aeinf)
The assessment of pharmacokinetic parameter of ASP8477 measured by Percentage of unchanged drug excreted into the urine from time of last measurable concentration (Aelast%) in urine
Time frame: Day 1 to Day 3
Percentage of unchanged drug excreted into the urine from time of last measurable concentration (Aelast%)
The assessment of pharmacokinetic parameter of ASP8477 measured by Percentage of unchanged drug excreted into the urine from time zero to infinity after single dose (Aeinf%) in urine
Time frame: Day 1 to Day 3
Percentage of unchanged drug excreted into the urine from time zero to infinity after single dose (Aeinf%)
The assessment of pharmacokinetic parameter of ASP8477 measured by Renal clearance (CLR) in urine
Time frame: Day 1 to Day 3
Renal clearance (CLR)
2 secondary outcomes
The assessment of pharmacokinetics of omeprazole measured by plasma concentration
Time frame: Day 1 to Day 3
The assessment of pharmacodynamics of ASP8477 measured by serum concentration
Time frame: Day 1 to Day 4
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2014.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Manager study chair
Astellas Pharma Europe B.V.
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ASP8477 and omeprazole in people with Pharmacokinetics of ASP8477 and Pharmacodynamics of ASP8477, run by Astellas Pharma Europe B.V. at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Belgium, France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety as assessed by recording adverse events, physical examination, laboratory assessments, vital signs, electrocardiograms (ECGs), cortisol levels, arterial carbon dioxide and oxygen saturation (time frame: Day1 to End of Study Visit (5-9 days after final discharge)). The study lists 14 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2014.