Healthy Volunteers Pharmacokinetic StudyPhase 1NCT01960374
Dose-escalation Study to Assess Selumetinib Safety, Tolerability and PK
A Phase 1 study testing Selumetinib in people with Healthy Volunteers Pharmacokinetic Study, run by AstraZeneca at 1 site in United Kingdom.
Trial summary
The purpose of the study is to assess the safety, tolerability and PK of selumetinib (AZD6244; ARRY-142886) (Hyd-Sulfate) in healthy male Japanese and non-Japanese Asian volunteers following administration of a single dose. Read more about this study
- Who is it for?
- Ages 18 to 55 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers Pharmacokinetic Study
- What is being tested?
- Selumetinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 117 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Oct 2013to May 2014
- 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 55 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Provision of signed and dated, written informed consent prior to any study-specific procedures.
- Non-smokers for at least three months prior to drug administration.
- Healthy male volunteers aged 18 to 55 years with suitable veins for cannulation or repeated venipunctures.
- Subjects included will be either healthy first generation Japanese, or healthy first generation non-Japanese Asian (e.g. Korean, Chinese).
- Japanese subjects must meet the following requirements in order to participate in the study:
- Subject was born in Japan, Parents and grandparents (both maternal and paternal) are Japanese
Show all 12Show fewer
- Subject is in possession of a valid Japanese passport, Expatriate of Japan for not longer than 5 years.
- Non-Japanese Asian subjects must meet the following requirements in order to participate in the study:
- Subject was born in an Asian country other than Japan, (such as Korea, China, Taiwan etc but not India), Parents and grandparents (both maternal and paternal) are non-Japanese Asian
- Subject is in possession of a valid passport from their country of origin, Expatriate of their country of origin for not longer than 5 years;
- Have a BMI between 18 and 30 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg, inclusive.
- Must use acceptable methods of contraception if the male subject's partner could become pregnant from the time of the first administration of treatment or study medication until 3 months following administration of the last treatment or dose of study medication.
Who cannot join
- History of any clinically important disease or disorder which, in the opinion of the investigator, may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer's ability to participate in the study
- History or presence of gastrointestinal, hepatic, or renal disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
- Any clinically significant abnormalities in clinical chemistry, haematology, or urinalysis results, as judged by the Investigator.
- Any positive result on screening for serum hepatitis B surface antigen (HbsAg), anti hepatitis core antibody (anti HBc Ig G [and anti HBc IgM if IgG is positive], hepatitis C antibodies (anti HCV), and HIV 1 and 2 antibodies (anti HIV 1/2).
- Abnormal vital signs, after 10 minutes supine rest.
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- Current or past history of central serous retinopathy or retinal vein thrombosis, intraocular pressure greater than 21 mmHg or uncontrolled glaucoma.
- Known or suspected history of drug abuse, as judged by the Investigator.
- History of alcohol abuse or excessive intake of alcohol, as judged by the Investigator.
- Positive screen for drugs of abuse or cotinine (nicotine) or positive screen for alcohol at screening or on admission to the study centre on Day -1.
- History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity to drugs with a similar chemical structure or class to selumetinib.
- Excessive intake of caffeine-containing drinks or food eg, coffee, tea, chocolate, Red Bull, or cola (more than 6 units of caffeine per day).
- Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks prior to the first administration of IP.
- Use of any prescribed or non prescribed medication including antacids, analgesics other than paracetamol/acetaminophen 1 g 4 times a day for occasional use, herbal remedies, vitamins, and minerals during the 2 weeks or five half-lives of the compound, whichever is longer, prior to the first administration of IP.
- Any intake of grapefruit, grapefruit juice, Seville oranges, Seville orange marmalade, or other products containing grapefruit or Seville oranges within 7 days of the first admission on Day -1.Plasma donation within 1 month of screening or any blood donation/blood loss greater than 500 mL during the 3 months prior to screening.
- Has received another new chemical entity (defined as a compound which has not been approved for marketing) or has participated in any other clinical study that included drug treatment within at least 3 months of the first administration of IP in this study.
- The period of exclusion begins 3 months after the final dose or 1 month after the last visit whichever is the longest. Note: volunteers consented and screened, but not randomized in this study or a previous Phase I study, are not excluded.Previous administration of study IP in the present study.- involvement in the planning and/or conduct of the study of any RPL/third party contractor or AstraZeneca employee and their close relatives regardless of their role in accordance with their internal procedures.- judged by the Investigator that the volunteer should not participate in the study if they have any ongoing or recent (i.e., during the screening period) minor medical complaints that may interfere with the interpretation of study data or are considered unlikely to comply with study procedures, restrictions, and requirements.-
- Volunteers who have previously received selumetinib.
- Volunteers who are vegans or have medical dietary restrictions.
- Volunteers who cannot communicate reliably with the Investigator.
- In addition, any of the following is regarded as criteria for exclusion from the genetic research: Previous bone marrow transplant, non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I, Single-centre, Open-label, Dose-escalation Study to Assess the Safety, Tolerability and Pharmacokinetics of Selumetinib Given Orally in Japanese and Non-Japanese Asian Healthy Male Volunteers
The purpose of the study is to assess the safety, tolerability and PK of selumetinib (AZD6244; ARRY-142886) (Hyd-Sulfate) in healthy male Japanese and non-Japanese Asian volunteers following administration of a single dose. Standard safety assessments including ECGs, vital signs, blood/urine safety tests, PK samples and monitoring of adverse events and an optional exploratory pharmacogenetics will be performed.
Read the detailed description
A Phase I, Single-centre, Open-label, Dose-escalation Study to Assess the Safety, Tolerability and Pharmacokinetics of Selumetinib (AZD6244; ARRY-142886) (Hyd-Sulfate) Given Orally in Japanese and Non-Japanese Asian Healthy Male Volunteers
- Conditions
- Healthy Volunteers Pharmacokinetic Study
- Being tested
- Selumetinib
- Keywords
- RAS or RAF oncogenes, Inhibition of MEK pathway, inhibition cancer cell proliferation promising anti-cancer therapeutic strategy.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SelumetinibDrug
Also called (AZD6244; ARRY-142886) (Hyd-Sulfate)
1, 2 or 3 x 25 mg selumetinib (AZD6244; ARRY-142886) (Hyd-Sulfate) capsule administered orally as a single dose on Day 1 of the study (total dose 25 mg, 50 mg and 75 mg respectively) with 240 ml of water at room temperature.
| Study group | Role | What they receive |
|---|---|---|
| Japanese Arm | Experimental | 3 cohorts of 9 subjects. Each cohort will receive oral 25 mg, 50 mg (anticipated) or 75 mg (anticipated) selumetinib (AZD6244; ARRY-142886) (Hyd-Sulfate). Receives: Drug: Selumetinib |
| Non-Japanese Asian Arm | Experimental | 3 cohorts of 9 subjects. Each cohort will receive oral 25 mg, 50 mg (anticipated) or 75 mg (anticipated) selumetinib (AZD6244; ARRY-142886) (Hyd-Sulfate). Receives: Drug: Selumetinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetics of selumetinib by assessment of maximum plasma selumetinib concentration (Cmax)
Rate and extent of absorption of selumetinib following oral doses of selumetinib by assessment of maximum plasma selumetinib concentration (Cmax). Metabolite to parent drug ratios will be calculated for the primary PK parameters AUC and Cmax, and AUC (0-t) if applicable.
Measured: Plasma will be collected at the following time points pre-dose then 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36 and 48 hours post dose
Pharmacokinetics of selumetinib by assessment of area under the plasma concentration time curve from zero to infinity (AUC)
Rate and extent of absorption of selumetinib following oral doses of selumetinib by assessment of area under the plasma concentration time curve from zero to infinity (AUC). Metabolite to parent drug ratios will be calculated for the primary PK parameters AUC and Cmax, and AUC (0-t) if applicable.
Measured: Plasma will be collected at the following time points pre-dose then 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36 and 48 hours post dose
Pharmacokinetics of selumetinib by assessment of area under the plasma concentration time curve from zero to the last measurable time point, AUC0-t, if AUC is not adequately measurable
Rate and extent of absorption of selumetinib following oral doses of selumetinib by assessment of area under the plasma concentration time curve from zero to the last measurable time point, AUC0-t, if AUC is not adequately measurable. Metabolite to parent drug ratios will be calculated for the primary PK parameters AUC and Cmax, and AUC (0-t) if applicable.
Measured: Plasma will be collected at the following time points pre-dose then 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36 and 48 hours post dose
Secondary outcomes (16)
Assessment of the Safety and Tolerability of Selumetinib by collection of adverse event reports
Assessment of adverse events (AEs) graded by Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Measured: All AEs will be collected from Day -1, throughout the treatment periods, and including the follow-up period, assessed after minimum of 7 days. SAEs will be recorded from the time of informed consent.
Pharmacogenetics
DNA samples may be used to explore how genetic variations may affect the response to selumetinib. PGx samples will be analysed for BCRP (breast cancer resistance protein), CYP2C19 (cytochrome P450 2C19) and UGT1A1 (UDP glucuronosyltransferase 1A1) genotypes. These transporter and enzymes are known to be polymorphic and maybe involved in the disposition of selumetinib. An assessment of subject's genotype for these transporter/enzymes and subjects PK will be made to see if there is any association of genotype and PK exposure.
Measured: Optional exploratory sample for pharmacogenetics can be taken any time between Day 1 and Day 3 after dosing.
Determine safety and tolerability of selumetinib by assessment of 12 lead electrocardiograms
Assessment of standard 12 lead electrocardiograms (ECGs)
Measured: Triplicate 12-lead ECG evaluated at screening & admission. Single 12-lead paper ECGs will follow all dECGs. Digital ECGs will be taken on Day 1 & Day 2 (pre-dose, 1.5h, 2.5h, 4h, 6h, 24h, 48h (pECG only)) & at follow up, at least 7 days after dose.
Determine safety and tolerability of selumetinib by physical examination
Assessment of physical examination
Measured: At screening and follow up (at least 7 days after dose) full physical examination will be performed. On admission and discharge (day 3) from the CPU a brief physical examination will be performed.
Determine safety and tolerability of selumetinib by assessment of vital signs
Assessment of standard vital signs (including blood pressure, pulse)
Measured: Supine blood pressure and pulse and oral body temperature will be evaluated at screening and admission, Day 1 (at pre-dose, 1.5h and 6h), Day 2, Day 3 and at follow up at follow up, at least 7 days after dose.
Determine safety and tolerability of selumetinib by assessment of clinical chemistry results
Assessment of lab parameters (clinical chemistry)
Measured: Clinical chemistry will be evaluated at screening, Day -1, Day 2 and at follow up, at least 7 days after dose.
Determine safety and tolerability of selumetinib by assessment of haematology results
Assessment of lab parameters (haematology)
Measured: Haematology will be evaluated at screening, Day -1, Day 2 and at follow up, at least 7 days after dose.
Determine safety and tolerability of selumetinib by assessment of urinalysis results
A sample for urinalysis to be collected along with the other clinical laboratory evaluations. Microscopy should only be performed if the urinalysis result is abnormal.
Measured: Urinalysis results will be evaluated at screening, Day-1 , Day 3 and follow up.
Determine safety and tolerability of selumetinib by assessment of opthalmic examination
Ophthalmic examination (best corrected visual acuity, IOP and slit-lamp fundoscopy) will be conducted at screening (will be considered the baseline value; no need to repeat) and for cause (on occurrence of AE only).
Measured: At baseline
Pharmacokinetics of selumetinib by assessment of area under the plasma concentration time curve from zero to the last measurable time point, AUC0-t.
Rate and extent of absorption of selumetinib following oral doses of selumetinib by assessment of area under the plasma concentration time curve from zero to the last measurable time point, AUC0-t. Metabolite to parent drug ratios will be calculated for the primary PK parameters AUC and Cmax, and AUC (0-t) if applicable.
Measured: Plasma will be collected at the following time points pre-dose then 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36 and 48 hours post dose
Pharmacokinetics of selumetinib by assessment of area under the plasma concentration time curve from zero to 12h time point, AUC0-12.
Rate and extent of absorption of selumetinib following oral doses of selumetinib by assessment of area under the plasma concentration time curve from zero to 12h time point, AUC0-12. Metabolite to parent drug ratios will be calculated for the primary PK parameters AUC and Cmax, and AUC (0-t) if applicable.
Measured: Plasma will be collected at the following time points pre-dose then 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36 and 48 hours post dose
Pharmacokinetics of selumetinib by assessment of area under the plasma concentration time curve from zero to 24h time point, AUC0-24.
Rate and extent of absorption of selumetinib following oral doses of selumetinib by assessment of area under the plasma concentration time curve from zero to 24h time point, AUC0-24. Metabolite to parent drug ratios will be calculated for the primary PK parameters AUC and Cmax, and AUC (0-t) if applicable.
Measured: Plasma will be collected at the following time points pre-dose then 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36 and 48 hours post dose
Pharmacokinetics of selumetinib by assessment of time to reach maximum plasma concentration for selumetinib (tmax).
Rate and extent of absorption of selumetinib following oral doses of selumetinib by assessment of time to reach maximum plasma concentration for selumetinib (tmax).
Measured: Plasma will be collected at the following time points pre-dose then 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36 and 48 hours post dose
Pharmacokinetics of selumetinib by assessment of selumetinib apparent clearance (CL/F).
Rate and extent of absorption of selumetinib following oral doses of selumetinib by assessment of of selumetinib apparent clearance (CL/F).
Measured: Plasma will be collected at the following time points pre-dose then 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36 and 48 hours post dose
Pharmacokinetics of selumetinib by assessment of rate of the elimination half-life of selumetinib from circulation following single oral dose (t½).
Rate and extent of absorption of selumetinib following oral doses of selumetinib by assessment of rate of the elimination half-life of selumetinib from circulation following single oral dose (t½).
Measured: Plasma will be collected at the following time points pre-dose then 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36 and 48 hours post dose
Pharmacokinetics of selumetinib by assessment of volume of distribution divided by bioavailability (Vss/F; estimate of steady state distribution volume for selumetinib following single oral dose).
Rate and extent of absorption of selumetinib following oral doses of selumetinib by assessment of volume of distribution divided by bioavailability (Vss/F; estimate of steady state distribution volume for selumetinib following single oral dose).
Measured: Plasma will be collected at the following time points pre-dose then 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36 and 48 hours post dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2013 (estimated)
- Study startOct 2013
- Primary completionMay 2014
- Study completionMay 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy Volunteers Pharmacokinetic StudyStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- 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
- Health services research
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 117 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ian C Smith, MD, Study chair, AstraZeneca UK, MSDUlrike Lorch, MD, Principal investigator, Richmond Pharmacology Ltd, UK
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01960374
- Sponsor's protocol ID
- D1532C00086
- Status last verified
- May 2014
- First submitted
- 9 Oct 2013
- Last updated
- 2 Jun 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Single-centre, Open-label, Dose-escalation Study to Assess the Safety, Tolerability and Pharmacokinetics of Selumetinib Given Orally in Japanese and Non-Japanese Asian Healthy Male Volunteers
- ClinicalTrials.gov ID
- NCT01960374
- Acronym / sponsor ID
- D1532C00086
- Conditions
- Healthy Volunteers Pharmacokinetic Study
- Keywords
- RAS or RAF oncogenes, Inhibition of MEK pathway, inhibition cancer cell proliferation promising anti-cancer therapeutic strategy.
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 117 participants (estimated)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- Oct 2013
- Primary completion
- May 2014 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 10 Oct 2013 (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 the study is to assess the safety, tolerability and PK of selumetinib (AZD6244; ARRY-142886) (Hyd-Sulfate) in healthy male Japanese and non-Japanese Asian volunteers following administration of a single dose. Standard safety assessments including ECGs, vital signs, blood/urine safety tests, PK samples and monitoring of adverse events and an optional exploratory pharmacogenetics will be performed.
Detailed description
A Phase I, Single-centre, Open-label, Dose-escalation Study to Assess the Safety, Tolerability and Pharmacokinetics of Selumetinib (AZD6244; ARRY-142886) (Hyd-Sulfate) Given Orally in Japanese and Non-Japanese Asian Healthy Male Volunteers
Study design
- Primary purpose
- Health services research
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Japanese Arm | Experimental | Drug: Selumetinib3 cohorts of 9 subjects. Each cohort will receive oral 25 mg, 50 mg (anticipated) or 75 mg (anticipated) selumetinib (AZD6244; ARRY-142886) (Hyd-Sulfate). |
| Non-Japanese Asian Arm | Experimental | Drug: Selumetinib3 cohorts of 9 subjects. Each cohort will receive oral 25 mg, 50 mg (anticipated) or 75 mg (anticipated) selumetinib (AZD6244; ARRY-142886) (Hyd-Sulfate). |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- Provision of signed and dated, written informed consent prior to any study-specific procedures.
- Non-smokers for at least three months prior to drug administration.
- Healthy male volunteers aged 18 to 55 years with suitable veins for cannulation or repeated venipunctures.
- Subjects included will be either healthy first generation Japanese, or healthy first generation non-Japanese Asian (e.g. Korean, Chinese).
- Japanese subjects must meet the following requirements in order to participate in the study:
Key exclusion criteria (21 listed)
- History of any clinically important disease or disorder which, in the opinion of the investigator, may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer's ability to participate in the study
- History or presence of gastrointestinal, hepatic, or renal disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
- Any clinically significant abnormalities in clinical chemistry, haematology, or urinalysis results, as judged by the Investigator.
- Any positive result on screening for serum hepatitis B surface antigen (HbsAg), anti hepatitis core antibody (anti HBc Ig G [and anti HBc IgM if IgG is positive], hepatitis C antibodies (anti HCV), and HIV 1 and 2 antibodies (anti HIV 1/2).
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 |
|---|---|---|
| SelumetinibAlso: (AZD6244; ARRY-142886) (Hyd-Sulfate)1, 2 or 3 x 25 mg selumetinib (AZD6244; ARRY-142886) (Hyd-Sulfate) capsule administered orally as a single dose on Day 1 of the study (total dose 25 mg, 50 mg and 75 mg respectively) with 240 ml of water at room temperature. | Drug | Japanese Arm, Non-Japanese Asian Arm |
Primary outcome
Pharmacokinetics of selumetinib by assessment of maximum plasma selumetinib concentration (Cmax)
Time frame: Plasma will be collected at the following time points pre-dose then 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36 and 48 hours post dose
Rate and extent of absorption of selumetinib following oral doses of selumetinib by assessment of maximum plasma selumetinib concentration (Cmax). Metabolite to parent drug ratios will be calculated for the primary PK parameters AUC and Cmax, and AUC (0-t) if applicable.
Pharmacokinetics of selumetinib by assessment of area under the plasma concentration time curve from zero to infinity (AUC)
Time frame: Plasma will be collected at the following time points pre-dose then 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36 and 48 hours post dose
Rate and extent of absorption of selumetinib following oral doses of selumetinib by assessment of area under the plasma concentration time curve from zero to infinity (AUC). Metabolite to parent drug ratios will be calculated for the primary PK parameters AUC and Cmax, and AUC (0-t) if applicable.
Pharmacokinetics of selumetinib by assessment of area under the plasma concentration time curve from zero to the last measurable time point, AUC0-t, if AUC is not adequately measurable
Time frame: Plasma will be collected at the following time points pre-dose then 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36 and 48 hours post dose
Rate and extent of absorption of selumetinib following oral doses of selumetinib by assessment of area under the plasma concentration time curve from zero to the last measurable time point, AUC0-t, if AUC is not adequately measurable. Metabolite to parent drug ratios will be calculated for the primary PK parameters AUC and Cmax, and AUC (0-t) if applicable.
16 secondary outcomes
Assessment of the Safety and Tolerability of Selumetinib by collection of adverse event reports
Time frame: All AEs will be collected from Day -1, throughout the treatment periods, and including the follow-up period, assessed after minimum of 7 days. SAEs will be recorded from the time of informed consent.
Pharmacogenetics
Time frame: Optional exploratory sample for pharmacogenetics can be taken any time between Day 1 and Day 3 after dosing.
Determine safety and tolerability of selumetinib by assessment of 12 lead electrocardiograms
Time frame: Triplicate 12-lead ECG evaluated at screening & admission. Single 12-lead paper ECGs will follow all dECGs. Digital ECGs will be taken on Day 1 & Day 2 (pre-dose, 1.5h, 2.5h, 4h, 6h, 24h, 48h (pECG only)) & at follow up, at least 7 days after dose.
Determine safety and tolerability of selumetinib by physical examination
Time frame: At screening and follow up (at least 7 days after dose) full physical examination will be performed. On admission and discharge (day 3) from the CPU a brief physical examination will be performed.
Determine safety and tolerability of selumetinib by assessment of vital signs
Time frame: Supine blood pressure and pulse and oral body temperature will be evaluated at screening and admission, Day 1 (at pre-dose, 1.5h and 6h), Day 2, Day 3 and at follow up at follow up, at least 7 days after dose.
Determine safety and tolerability of selumetinib by assessment of clinical chemistry results
Time frame: Clinical chemistry will be evaluated at screening, Day -1, Day 2 and at follow up, at least 7 days after dose.
Determine safety and tolerability of selumetinib by assessment of haematology results
Time frame: Haematology will be evaluated at screening, Day -1, Day 2 and at follow up, at least 7 days after dose.
Determine safety and tolerability of selumetinib by assessment of urinalysis results
Time frame: Urinalysis results will be evaluated at screening, Day-1 , Day 3 and follow up.
Determine safety and tolerability of selumetinib by assessment of opthalmic examination
Time frame: At baseline
Pharmacokinetics of selumetinib by assessment of area under the plasma concentration time curve from zero to the last measurable time point, AUC0-t.
Time frame: Plasma will be collected at the following time points pre-dose then 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36 and 48 hours post dose
Pharmacokinetics of selumetinib by assessment of area under the plasma concentration time curve from zero to 12h time point, AUC0-12.
Time frame: Plasma will be collected at the following time points pre-dose then 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36 and 48 hours post dose
Pharmacokinetics of selumetinib by assessment of area under the plasma concentration time curve from zero to 24h time point, AUC0-24.
Time frame: Plasma will be collected at the following time points pre-dose then 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36 and 48 hours post dose
Pharmacokinetics of selumetinib by assessment of time to reach maximum plasma concentration for selumetinib (tmax).
Time frame: Plasma will be collected at the following time points pre-dose then 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36 and 48 hours post dose
Pharmacokinetics of selumetinib by assessment of selumetinib apparent clearance (CL/F).
Time frame: Plasma will be collected at the following time points pre-dose then 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36 and 48 hours post dose
Pharmacokinetics of selumetinib by assessment of rate of the elimination half-life of selumetinib from circulation following single oral dose (t½).
Time frame: Plasma will be collected at the following time points pre-dose then 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36 and 48 hours post dose
Pharmacokinetics of selumetinib by assessment of volume of distribution divided by bioavailability (Vss/F; estimate of steady state distribution volume for selumetinib following single oral dose).
Time frame: Plasma will be collected at the following time points pre-dose then 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36 and 48 hours post dose
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 2 Jun 2014.
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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.
Ian C Smith, MD study chair
AstraZeneca UK, MSD
Ulrike Lorch, MD principal investigator
Richmond Pharmacology Ltd, UK
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Selumetinib in people with Healthy Volunteers Pharmacokinetic Study, run by AstraZeneca at 1 site in United Kingdom.
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 12 inclusion and 21 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 2 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in 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. 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?
Pharmacokinetics of selumetinib by assessment of maximum plasma selumetinib concentration (Cmax) (time frame: Plasma will be collected at the following time points pre-dose then 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36 and 48 hours post dose). The study lists 3 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 2 Jun 2014.