Healthy VolunteersPhase 1NCT02420782
First-in-human: Single Ascending Dose, Food Effect, Drug-drug Interaction, Multiple Ascending Dose, Proof of Pharmacology
A Phase 1 study testing ASP6282, Itraconazole and Pilocarpine in people with Healthy Volunteers, run by Astellas Pharma Europe B.V. at 2 sites in 2 countries.
Trial summary
The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics (PK) and pharmacodynamics (PD) of single and multiple ascending oral doses of ASP6282 in healthy male and female subjects. 1 cohort (elderly) receives also a midazolam dosing. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- ASP6282, Itraconazole and Pilocarpine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 116 participants
- Where
- 2 sitesin 2 countries
- Study dates
- May 2015to May 2016
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Subject has a body mass index (BMI) range of 18.5 to 30.0 kg/m2, inclusive. The subject weighs at least 50 kg [screening].
- Female subject must not donate ova starting at screening and throughout the clinical study period, and for 28 days after the final study drug administration.
- Male subject and his female spouse/partners who are of childbearing potential must be using highly effective contraception consisting of 2 forms of birth control (1 of which must be a barrier method) starting at screening and continue throughout the clinical study period, and for 90 days after the final study drug administration.
- Male subject must not donate sperm starting at screening and throughout the clinical study period, and for 90 days after last study drug administration.
- Subject agrees not to participate in another interventional study while participating in the present clinical study, defined as signing the informed consent form until completion of the last study visit.
- Germany only:
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- Female subject must either:
- Be of nonchildbearing potential:
- Postmenopausal (defined as at least 1 year without any menses) prior to screening, or,
- Documented surgically sterile.
- Or, if of childbearing potential:
- Agree not to try to become pregnant during the clinical study and for 90 days after the final study drug administration,
- Must have a negative serum pregnancy test at day -1, and
- If heterosexually active, agree to consistently use a form of highly effective birth control in combination with a barrier method starting at screening and continuing throughout the clinical study period, and for 90 days after the final study drug administration.
- Or agree to stay abstinent, if abstinence is the preferred and usual lifestyle of the subject, starting at screening and continuing throughout the clinical study period and for 90 days after the final study drug administration.
- Female subject must agree not to breastfeed starting at screening and throughout the clinical study period, and for 90 days after the final study drug administration.
- Female subject must not donate ova starting at screening and throughout the clinical study period, and for 90 days after the final study drug administration.
Who cannot join
- Female subject who has been pregnant within 6 months prior to screening assessment or breastfeeding within 3 months prior to screening.
- Subject has a known or suspected hypersensitivity to ASP6282, itraconazole (part 1 - DDI only) or pilocarpine (part 3 - Proof of pharmacology (PoP) only) or any components of the formulations used.
- Subject uses a CYP3A4 metabolized substrate that can prolong the QT interval, e.g., astemizole, bepridil, cisapride, dofetilide, levacetylmethadol (levomethadyl), mizolastine, pimozide, quinidine, sertindole and terfenadine.
- Subject uses any of the following medication: atorvastatin, lovastatin and simvastatin, triazolam, midazolam, ergot alkaloids such as dihydroergotamine, ergometrine (ergonovine), ergotamine and methylergometrine (methylergonovine), eletriptan and nisodipine.
- Subject with evidence of ventricular dysfunction such as congestive heart failure or a history of congestive heart failure.
- Subject has clinically significant, cardiorenal disease, asthma and/or any other disease at risk for cholinergic agonists.
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- Subject has a condition of the eye which could be affected by the intake of pilocarpine (e.g., acute iritis) (part 3 - PoP only).
- Subject has any of the liver chemistry tests (Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), Total bilirubin (TBL) above the Upper limit of normal (ULN)). In such a case, the assessment may be repeated once on Day -1 (in part 1 - DDI: treatment period 1 only).
- Subject has any clinically significant history of allergic conditions (including drug allergies, asthma, eczema or anaphylactic reactions, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).
- Subject has chronic bronchitis and/or chronic obstructive pulmonary disease, or known or suspected cholelithiasis or biliary tract disease, or peptic ulceration or cognitive or psychiatric disturbances, or renal or hepatic insufficiency, or narrow-angle glaucoma.
- Subject has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection) or fungal (noncutaneous) infection within 1 week prior to admission to the clinical unit on Day -1.
- Subject has any clinically significant abnormality following the investigator's review of the physical examination, ECG and clinical study protocol-defined clinical laboratory tests at screening or day -1.
- Subject has a mean pulse < 40 or > 90 bpm; mean systolic blood pressure (SBP) > 140 mmHg; mean diastolic blood pressure (DBP) > 90 mmHg (vital signs measurements taken in triplicate after subject has been resting in supine position for 5 minutes; pulse will be measured automatically) on admission to the clinical unit on Day -1. If the mean blood pressure exceeds the limits above, 1 additional triplicate can be taken.
- Subject has a mean corrected QT interval using Fridericia's formula (QTcF) > 430 ms (for male subjects) and > 450 ms (for female subjects) at screening. If the mean QTcF exceeds the limits above, 1 additional triplicate ECG can be taken at screening.
- Subject uses any prescribed or nonprescribed drugs (including vitamins, natural and herbal remedies, e.g., St. John's wort) in the 2 weeks prior to first study drug administration, except for occasional use of paracetamol (up to 2 g/day) (all parts) and except for use of contraceptives or hormone replacement therapy (except for part 1- DDI).
- Subject has a history of smoking within 6 months prior to first study drug administration on day 1.
- Subject has a history of drinking > 21 units of alcohol/week for male subjects or > 14 units of alcohol/week for female subjects (1 unit = 10 g pure alcohol = 250 mL of beer [5%] or 35 mL of spirits [35%] or 100 mL of wine [12%]) within 3 months prior to admission to the clinical unit on Day -1.
- Subject has consumed grapefruit/Seville oranges, grapefruit-containing products or Seville orange-containing products within 72 hours prior to admission to the clinical unit on Day -1.
- Subject uses any inducer of metabolism (e.g., barbiturates, rifampin) within 1 month prior to admission to the clinical unit on Day -1.
- Subject uses any drugs of abuse within 3 months prior to admission to the clinical unit on Day -1.
- Subject had significant blood loss, donated 1 unit (500 mL) of blood or more, or received a transfusion of any blood or blood products within 60 days or donated plasma within 7 days prior to admission to the clinical unit on Day -1.
- Subject has a positive serology test for hepatitis B surface antigen (HBsAg), hepatitis A virus antibodies (anti-HAV) (immunoglobulin M [IgM]), hepatitis C virus antibodies (anti-HCV), or antibodies to human immunodeficiency virus type 1 (HIV-1) and/or type 2 (HIV-2) at screening.
- Subject participated in any clinical study or has been treated with any investigational drugs within 90 days prior to screening.
- Germany only:
- Subject has a mean pulse < 50 or > 90 bpm; mean systolic blood pressure (SBP) > 140 mmHg; mean diastolic blood pressure (DBP) > 90 mmHg (vital signs measurements taken in triplicate after subject has been resting in supine position for 5 minutes; pulse will be measured automatically) on admission to the clinical unit on day -1. (For elderly subjects the following criteria apply: SBP > 160 mmHg and DBP > 100 mmHg). If the mean blood pressure exceeds the limits above, 1 additional triplicate can be taken.
- Subject has a mean corrected QT interval using Fridericia's formula (QTcF) > 430 ms (for male subjects) and > 450 ms (for female subjects) at day -1. If the mean QTcF exceeds the limits above, 1 additional triplicate ECG can be taken at day -1.
- Subject has a positive serology test for hepatitis B surface antigen (HBsAg), hepatitis B core antibodies, hepatitis A virus antibodies (anti-HAV) (immunoglobulin M [IgM]), hepatitis C virus antibodies (anti-HCV), or antibodies to human immunodeficiency virus type 1 (HIV-1) and/or type 2 (HIV-2) at screening.
- Subject is unable to communicate, read and understand German, or has any other condition which, in the investigator's opinion, makes the subject unsuitable for clinical study participation.
- Subject is a vulnerable subject (e.g., subject kept in detention).
- Subject has a known or suspected hypersensitivity to ASP6282, itraconazole (part 1 - DDI only), pilocarpine (part 3 - PoP only) or midazolam (part 2 - elderly cohort only) or any components of the formulations used.
- Subject uses any prescribed or nonprescribed drugs (including vitamins, natural and herbal remedies, e.g., St. John's wort) in the 2 weeks prior to first study drug administration, except for occasional use of paracetamol (up to 2 g/day) (all parts) and except for use of hormone replacement therapy (except for part 1 - DDI).
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: A Phase 1 Combined Single and Multiple Ascending Oral Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ASP6282 in Healthy Nonelderly and Elderly Male and Female Subjects, Including a Food Effect Cohort and Drug-drug Interaction Cohort With Itraconazole
The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics (PK) and pharmacodynamics (PD) of single and multiple ascending oral doses of ASP6282 in healthy male and female subjects. 1 cohort (elderly) receives also a midazolam dosing.
This study will also explore the effect of itraconazole (another drug) on the PK of ASP6282, as well as to evaluate the safety and tolerability of ASP6282 alone and in combination with itraconazole in healthy male and female subjects.
Also, this study is to evaluate the PD and PK effects of single oral doses of ASP6282 on pilocarpine-induced salivation and pupil diameter in healthy nonelderly male and female subjects.
Read the detailed description
This study consists of three parts. Part 1 is Single Ascending Dose Including Food Effect and Drug-drug Interaction (DDI) with Itraconazole. There will be a washout between treatment period 1 and 2 in the DDI arm of Part 1; Part 2 is a Multiple Ascending Dose (MAD); Part 3, with a treatment period 1, 2 and 3 is Proof of Pharmacology. There will be a washout between each treatment period
- Conditions
- Healthy Volunteers
- Being tested
- ASP6282, Itraconazole, Pilocarpine, Placebo, Midazolam
- Keywords
- Pharmacokinetics, ASP6282, Pharmacodynamics, Drug-drug interaction, Midazolam, Safety and tolerability, Healthy volunteers, Itraconazole
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ASP6282Drug
oral
ItraconazoleDrug
oral
PilocarpineDrug
oral
PlaceboDrug
oral
MidazolamDrug
Also called Versed
oral
| Study group | Role | What they receive |
|---|---|---|
| ASP6282 single ascending dose (fasted) | Experimental | Part 1 Receives: Drug: ASP6282 |
| Placebo single ascending dose (fasted) | Placebo comparator | Part 1 Receives: Drug: Placebo |
| ASP6282 single dose (fed) | Experimental | Part 1 Receives: Drug: ASP6282 |
| Placebo single dose (fed) | Placebo comparator | Part 1 Receives: Drug: Placebo |
| ASP6282 single dose (fasted) | Experimental | Part 1 Period 1 Receives: Drug: ASP6282 |
| Itraconazole multiple dose and ASP6282 single dose (fasted) | Experimental | Part 1 Period 2 Receives: Drug: ASP6282; Drug: Itraconazole |
| ASP6282 multiple ascending dose (nonelderly and elderly) | Experimental | Part 2. Germany only: once daily dosing, optional twice daily dosing. Midazolam dosing elderly only, exploratory for DDI purpose Receives: Drug: ASP6282; Drug: Midazolam |
| Placebo multiple ascending dose (nonelderly and elderly) | Placebo comparator | Part 2. Germany only: once daily dosing, optional twice daily dosing Receives: Drug: Placebo |
| ASP6282 and pilocarpine | Experimental | Part 3 Receives: Drug: ASP6282; Drug: Pilocarpine |
| Placebo and pilocarpine | Other | Part 3 Receives: Drug: Pilocarpine; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety as assessed by adverse events
Measured: Part 1: up to 10 days; Part 2 up to 18 days
Safety as assessed by vital signs
Vital signs include: blood pressure, pulse rate and body temperature
Measured: Part 1: up to 10 days; Part 2 up to 18 days
Safety as assessed by safety laboratory tests
Laboratory tests include: hematology, biochemistry and urinalysis
Measured: Part 1: up to 10 days; Part 2 up to 18 days
Safety as assessed by electrocardiogram (ECG) measurements (Part 1)
ECG measurements include routine ECG
Measured: From screening to end of study visit (ESV) (up to day 10)
Safety as assessed by continuous cardiac monitoring (Part 1)
12- lead ECG continuous cardiac monitoring, real-time cardiac monitoring (telemetry), cardiac troponin
Measured: From day 1 up to day 5
Safety as assessed by electrocardiogram (ECG) measurements (Part 2)
ECG measurements include routine 12- lead ECG, cardiac troponin
Measured: From screening to ESV (Up to day 18)
Safety as assessed by continuous electrocardiogram (ECG) measurements (Part 2)
Twelve lead continuous cardiac monitoring, cardiac troponin
Measured: From screening up to day 15
Safety as assessed by the Orthostatic challenge test (OCT) (Part 1)
Blood pressure measurement
Measured: From day -1 up to day 5
Pharmacodynamic parameter salivary secretion at specified timepoints (Part 3)
Measured (mg/min) salivary secretion at specific timepoints
Measured: Day 1, each treatment period
Pharmacodynamic parameter salivary secretion AUEsal (Part 3)
Area under the effect curve salivary secretion (AUEsal)
Measured: Day 1, each treatment period
Pharmacodynamic parameter salivary secretion Emax,sal (Part 3)
Maximum pharmacodynamic effect salivary secretion (Emax,sal)
Measured: Day 1, each treatment period
Pharmacodynamic parameter salivary secretion tmax,sal (Part 3)
Time at maximum concentration salivary secretion (tmax,sal)
Measured: Day 1, each treatment period
Secondary outcomes (11)
Pharmacokinetics profile of ASP6282 (plasma): AUCinf, AUClast, Cmax, CL/F, tlag, tmax, t½, Vz/F (Part 1)
Area under the concentration-time curve from the time of dosing extrapolated to time infinity (AUCinf); Area under the concentration-time curve from the time of dosing to the last measurable concentration (AUClast); Maximum concentration (Cmax); Apparent total systemic clearance after extravascular dosing (CL/F); Time prior to the time corresponding to the first measurable (nonzero) concentration (tlag);Time at maximum concentration (tmax); Terminal elimination half-life (t½); Apparent volume of distribution during the terminal elimination phase after extravascular dosing (Vz/F)
Measured: Day 1 up to Day 5, each treatment period
Pharmacokinetics profile of ASP6282 (urine): Aelast, Aelast%, Aeinf, Aeinf%, CLR (Part 1)
Cumulative amount of study drug excreted into urine from time of dosing up to the collection time of the last measurable concentration (Aelast); Percentage of study drug dose excreted into urine from time of dosing up to the collection time of the last measurable concentration (Aelast%); Cumulative amount of study drug excreted into urine from time of dosing extrapolated to time infinity (Aeinf); Percentage of study drug dose excreted into urine from time of dosing extrapolated to time infinity (Aeinf%); Renal clearance (CLR)
Measured: Day 1 up to Day 4, each treatment period
Pharmacokinetic parameter of Itraconazole (plasma) Ctrough (Part 1)
DDI arm only. Concentration immediately prior to dosing at multiple dosing (Ctrough)
Measured: Day 1 up to Day 5, each treatment period
Pharmacokinetics profile of ASP6282 (plasma): AUC24, tlag, AUCtau, CL/F, PTR, Rac(AUC), Cmax, tmax, t½, Vz/F (Part 2)
Area under the concentration-time curve from the time of dosing to 24 hours postdose (AUC24); Area under the concentration-time curve from the time of dosing to the start of the next dosing interval (AUCtau); Peak trough ratio (PTR), Accumulation ratio calculated using the area under the concentration-time curve (Rac(AUC))
Measured: Day 1 up to Day 20
Pharmacokinetics profile of ASP6282 (urine): Aetau, Aetau%, CLR (Part 2)
Percentage of study drug dose excreted into urine over the time interval between consecutive dosing (Aetau%)
Measured: Day 14
Pharmacokinetics profile of ASP6282 (plasma): AUC6, AUCinf, AUClast, Cmax, CL/F, tlag, tmax, t½, Vz/F (Part 3)
Area under the concentration-time curve from the time of dosing to 6 hours Postdose (AUC6)
Measured: Day 1 up to Day 5, per treatment period
Pharmacokinetics profile of Pilocarpine (plasma): AUC6, Cmax, tmax (Part 3)
Measured: Day 1, per treatment period
Pharmacodynamic profile pupil diameter pupS, AUEpupS, Emax,pupS, tmax,pupS, (Part 1, Part 2)
Part 1: exclusive DDI arm. Pupil diameter, scotopic lighting condition (pupS); Area under the effect curve pupil diameter, scotopic lighting condition (AUEpupS); Maximum pharmacodynamic effect pupil diameter, scotopic lighting condition (Emax,pupS), Time at maximum concentration pupil diameter, scotopic lighting condition (tmax,pupS)
Measured: Part 1: Day 1; Part 2: Day -1 and Day 14
Pharmacodynamic profile salivary secretion AUEsal, Emax,sal, tmax,sal (Part 1, Part 2)
Part 1: exclusive DDI arm
Measured: Part 1: Screening and Day 1; Part 2: Day -1 and Day 14
Pharmacodynamic profile of Bond and Lader VAS (Part 1, Part 2)
Visual analogue scale (VAS)
Measured: Part 1: Day 1; Part 2: Day -1 and Day 14
Safety profile assessed by nature, frequency and severity of adverse events, vital signs, safety laboratory tests and 12 lead ECG (Part 3)
Measured: Screening, Day -1 and ESV (Day 10)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2015 (estimated)
- Study startMay 2015
- Primary completionMay 2016
- Study completionMay 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy VolunteersStudies 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
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 116 participants (actual)
Sponsor and investigators
- Lead sponsor
- Astellas Pharma Europe B.V.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Study director, Clinical Pharmacology & Exploratory Development (CPED)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02420782
- Sponsor's protocol ID
- 6282-CL-0001
- Other IDs
- 2015-000093-35, 2015
- Status last verified
- Jun 2016
- First submitted
- 15 Apr 2015
- Last updated
- 1 Jul 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Combined Single and Multiple Ascending Oral Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ASP6282 in Healthy Nonelderly and Elderly Male and Female Subjects, Including a Food Effect Cohort and Drug-drug Interaction Cohort With Itraconazole
- ClinicalTrials.gov ID
- NCT02420782
- Acronym / sponsor ID
- 6282-CL-0001
- Conditions
- Healthy Volunteers
- Keywords
- Pharmacokinetics, ASP6282, Pharmacodynamics, Drug-drug interaction, Midazolam, Safety and tolerability, Healthy volunteers, Itraconazole
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 116 participants (actual)
- Lead sponsor
- Astellas Pharma Europe B.V.Industry (pharma, biotech, devices)
- Study start
- May 2015
- Primary completion
- May 2016 (actual)
- Study completion
- May 2016 (actual)
- First posted
- 20 Apr 2015 (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.
The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics (PK) and pharmacodynamics (PD) of single and multiple ascending oral doses of ASP6282 in healthy male and female subjects. 1 cohort (elderly) receives also a midazolam dosing.
This study will also explore the effect of itraconazole (another drug) on the PK of ASP6282, as well as to evaluate the safety and tolerability of ASP6282 alone and in combination with itraconazole in healthy male and female subjects.
Also, this study is to evaluate the PD and PK effects of single oral doses of ASP6282 on pilocarpine-induced salivation and pupil diameter in healthy nonelderly male and female subjects.
Detailed description
This study consists of three parts. Part 1 is Single Ascending Dose Including Food Effect and Drug-drug Interaction (DDI) with Itraconazole. There will be a washout between treatment period 1 and 2 in the DDI arm of Part 1; Part 2 is a Multiple Ascending Dose (MAD); Part 3, with a treatment period 1, 2 and 3 is Proof of Pharmacology. There will be a washout between each treatment period
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 10
| Arm | Type | Receives |
|---|---|---|
| ASP6282 single ascending dose (fasted) | Experimental | Drug: ASP6282Part 1 |
| Placebo single ascending dose (fasted) | Placebo comparator | Drug: PlaceboPart 1 |
| ASP6282 single dose (fed) | Experimental | Drug: ASP6282Part 1 |
| Placebo single dose (fed) | Placebo comparator | Drug: PlaceboPart 1 |
| ASP6282 single dose (fasted) | Experimental | Drug: ASP6282Part 1 Period 1 |
| Itraconazole multiple dose and ASP6282 single dose (fasted) | Experimental | Drug: ASP6282, Drug: ItraconazolePart 1 Period 2 |
| ASP6282 multiple ascending dose (nonelderly and elderly) | Experimental | Drug: ASP6282, Drug: MidazolamPart 2. Germany only: once daily dosing, optional twice daily dosing. Midazolam dosing elderly only, exploratory for DDI purpose |
| Placebo multiple ascending dose (nonelderly and elderly) | Placebo comparator | Drug: PlaceboPart 2. Germany only: once daily dosing, optional twice daily dosing |
| ASP6282 and pilocarpine | Experimental | Drug: ASP6282, Drug: PilocarpinePart 3 |
| Placebo and pilocarpine | Other | Drug: Pilocarpine, Drug: PlaceboPart 3 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Subject has a body mass index (BMI) range of 18.5 to 30.0 kg/m2, inclusive. The subject weighs at least 50 kg [screening].
- Female subject must not donate ova starting at screening and throughout the clinical study period, and for 28 days after the final study drug administration.
- Male subject and his female spouse/partners who are of childbearing potential must be using highly effective contraception consisting of 2 forms of birth control (1 of which must be a barrier method) starting at screening and continue throughout the clinical study period, and for 90 days after the final study drug administration.
- Male subject must not donate sperm starting at screening and throughout the clinical study period, and for 90 days after last study drug administration.
- Subject agrees not to participate in another interventional study while participating in the present clinical study, defined as signing the informed consent form until completion of the last study visit.
Key exclusion criteria (31 listed)
- Female subject who has been pregnant within 6 months prior to screening assessment or breastfeeding within 3 months prior to screening.
- Subject has a known or suspected hypersensitivity to ASP6282, itraconazole (part 1 - DDI only) or pilocarpine (part 3 - Proof of pharmacology (PoP) only) or any components of the formulations used.
- Subject uses a CYP3A4 metabolized substrate that can prolong the QT interval, e.g., astemizole, bepridil, cisapride, dofetilide, levacetylmethadol (levomethadyl), mizolastine, pimozide, quinidine, sertindole and terfenadine.
- Subject uses any of the following medication: atorvastatin, lovastatin and simvastatin, triazolam, midazolam, ergot alkaloids such as dihydroergotamine, ergometrine (ergonovine), ergotamine and methylergometrine (methylergonovine), eletriptan and nisodipine.
- Subject with evidence of ventricular dysfunction such as congestive heart failure or a history of congestive heart failure.
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 |
|---|---|---|
| ASP6282oral | Drug | ASP6282 and pilocarpine, ASP6282 multiple ascending dose (nonelderly and elderly), ASP6282 single ascending dose (fasted), ASP6282 single dose (fasted), ASP6282 single dose (fed), Itraconazole multiple dose and ASP6282 single dose (fasted) |
| Itraconazoleoral | Drug | Itraconazole multiple dose and ASP6282 single dose (fasted) |
| Pilocarpineoral | Drug | ASP6282 and pilocarpine, Placebo and pilocarpine |
| Placebooral | Drug | Placebo and pilocarpine, Placebo multiple ascending dose (nonelderly and elderly), Placebo single ascending dose (fasted), Placebo single dose (fed) |
| MidazolamAlso: Versedoral | Drug | ASP6282 multiple ascending dose (nonelderly and elderly) |
Primary outcome
Safety as assessed by adverse events
Time frame: Part 1: up to 10 days; Part 2 up to 18 days
Safety as assessed by vital signs
Time frame: Part 1: up to 10 days; Part 2 up to 18 days
Vital signs include: blood pressure, pulse rate and body temperature
Safety as assessed by safety laboratory tests
Time frame: Part 1: up to 10 days; Part 2 up to 18 days
Laboratory tests include: hematology, biochemistry and urinalysis
Safety as assessed by electrocardiogram (ECG) measurements (Part 1)
Time frame: From screening to end of study visit (ESV) (up to day 10)
ECG measurements include routine ECG
Safety as assessed by continuous cardiac monitoring (Part 1)
Time frame: From day 1 up to day 5
12- lead ECG continuous cardiac monitoring, real-time cardiac monitoring (telemetry), cardiac troponin
Safety as assessed by electrocardiogram (ECG) measurements (Part 2)
Time frame: From screening to ESV (Up to day 18)
ECG measurements include routine 12- lead ECG, cardiac troponin
Safety as assessed by continuous electrocardiogram (ECG) measurements (Part 2)
Time frame: From screening up to day 15
Twelve lead continuous cardiac monitoring, cardiac troponin
Safety as assessed by the Orthostatic challenge test (OCT) (Part 1)
Time frame: From day -1 up to day 5
Blood pressure measurement
Pharmacodynamic parameter salivary secretion at specified timepoints (Part 3)
Time frame: Day 1, each treatment period
Measured (mg/min) salivary secretion at specific timepoints
Pharmacodynamic parameter salivary secretion AUEsal (Part 3)
Time frame: Day 1, each treatment period
Area under the effect curve salivary secretion (AUEsal)
Pharmacodynamic parameter salivary secretion Emax,sal (Part 3)
Time frame: Day 1, each treatment period
Maximum pharmacodynamic effect salivary secretion (Emax,sal)
Pharmacodynamic parameter salivary secretion tmax,sal (Part 3)
Time frame: Day 1, each treatment period
Time at maximum concentration salivary secretion (tmax,sal)
11 secondary outcomes
Pharmacokinetics profile of ASP6282 (plasma): AUCinf, AUClast, Cmax, CL/F, tlag, tmax, t½, Vz/F (Part 1)
Time frame: Day 1 up to Day 5, each treatment period
Pharmacokinetics profile of ASP6282 (urine): Aelast, Aelast%, Aeinf, Aeinf%, CLR (Part 1)
Time frame: Day 1 up to Day 4, each treatment period
Pharmacokinetic parameter of Itraconazole (plasma) Ctrough (Part 1)
Time frame: Day 1 up to Day 5, each treatment period
Pharmacokinetics profile of ASP6282 (plasma): AUC24, tlag, AUCtau, CL/F, PTR, Rac(AUC), Cmax, tmax, t½, Vz/F (Part 2)
Time frame: Day 1 up to Day 20
Pharmacokinetics profile of ASP6282 (urine): Aetau, Aetau%, CLR (Part 2)
Time frame: Day 14
Pharmacokinetics profile of ASP6282 (plasma): AUC6, AUCinf, AUClast, Cmax, CL/F, tlag, tmax, t½, Vz/F (Part 3)
Time frame: Day 1 up to Day 5, per treatment period
Pharmacokinetics profile of Pilocarpine (plasma): AUC6, Cmax, tmax (Part 3)
Time frame: Day 1, per treatment period
Pharmacodynamic profile pupil diameter pupS, AUEpupS, Emax,pupS, tmax,pupS, (Part 1, Part 2)
Time frame: Part 1: Day 1; Part 2: Day -1 and Day 14
Pharmacodynamic profile salivary secretion AUEsal, Emax,sal, tmax,sal (Part 1, Part 2)
Time frame: Part 1: Screening and Day 1; Part 2: Day -1 and Day 14
Pharmacodynamic profile of Bond and Lader VAS (Part 1, Part 2)
Time frame: Part 1: Day 1; Part 2: Day -1 and Day 14
Safety profile assessed by nature, frequency and severity of adverse events, vital signs, safety laboratory tests and 12 lead ECG (Part 3)
Time frame: Screening, Day -1 and ESV (Day 10)
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 1 Jul 2016.
- Individual participant dataSharing planned: Undecided
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Screening Protocol
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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.
Medical Monitor study director
Clinical Pharmacology & Exploratory Development (CPED)
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 ASP6282, Itraconazole and Pilocarpine in people with Healthy Volunteers, 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 17 inclusion and 31 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 1 Jul 2016. 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 Germany, United Kingdom. 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. Some participants in this study may receive a placebo. 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 adverse events (time frame: Part 1: up to 10 days; Part 2 up to 18 days). The study lists 12 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 1 Jul 2016.