To Assess the Pharmacokinetics, Safety and Tolerability of Selumetinib in Renal Impaired Subjects and Healthy Subjects

NCT02063204 | Completed Phase 1

• 1 other identifier: D1532C00081
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

A study to assess the pharmacokinetics, safety and tolerability of Selumetinib (AZD6244, ARRY-142886) in subjects with renal impairment and healthy subjects

Conditions

Solid Tumours

Keywords

Phase I, healthy, pharmacokinetics, renal impairment

Outcome Measures

Primary Outcomes (3)

• Description of the pharmacokinetic(PK) profile in terms of maximum observed plasma concentration (Cmax)

  This will be taken at visit 2 for Healthy volunteers and at visit 2 and 3 for patients with end stage renal disease

  Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h

• Description of PK profile in terms of area under plasma concentration-time curve from zero extrapolated to infinity (AUC)

  This will be taken at visit 2 for Healthy volunteers and at visit 2 and 3 for patients with end stage renal disease

  Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h

• Description of PK profile in terms of area under plasma concentration-time curve to time of last measurable concentration (AUC[0-t]) for selumetinib if AUC is not reportable in more than 80% of subjects

  This will be taken at visit 2 for Healthy volunteers and at visit 2 and 3 for patients with end stage renal disease

  Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h

Secondary Outcomes (11)

• Description of the safety profile in terms of adverse events, physical examinations, ophthalmologic assessments, vital signs, clinical laboratory assessments and 12-lead electrocardiograms.

  From screening until follow up. Approximately 6 weeks for healthy volunteers and 8 weeks for renal patients

• Description of the PK profile in terms of time to reach maximum observed concentration administration (tmax)

  Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h

• Description of PK profile in terms of area under the plasma concentration time curve from zero to 12 hours postdose (AUC[0-12])

  Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h, and12h

• Description of PK profile in terms of terminal rate constant (λz), terminal elimination half-life (t1/2), apparent oral clearance (CL/F)

  Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h

• Description of PK profile in terms of apparent volume of distribution at steady state (Vss/F) and apparent volume of distribution during the terminal phase (Vz/F)

  Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h

Study Arms (3)

HV selumetinib Stage 1

EXPERIMENTAL

Healthy volunteer (HV)group to receive selumetinib 50mg (2x25mg) orally

Drug: selumetinib

ESRD selumetinib Stage 1

EXPERIMENTAL

End stage renal disease (ESRD)patients to recieve selumetinib 50mg (2x25mg) orally

Drug: selumetinib

Selumetinib stage 2

EXPERIMENTAL

If deemed necessary patients with mild and/or moderate and/or severe renal impairment will recieve selumetinib 50mg(2x25mg) orally

Drug: selumetinib

Interventions

selumetinib DRUG

selumetinib 50 mg (2x25mg) administered by mouth as capsules

ESRD selumetinib Stage 1; HV selumetinib Stage 1; Selumetinib stage 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female (non childbearing potential) subjects aged 18 years or more with suitable veins for cannulation or repeated venipuncture.
• Have a weight of at least 50 kg (110 lbs) and body mass index (BMI) between 18 and 40 kg/m2, inclusive.
• Must be in good health as determined by a medical history, physical examination, 12 lead ECG, clinical laboratory evaluations, and an ophthalmic examination performed before the administration of the investigational product.
• Stable renal function

You may not qualify if:

• Subjects of Japanese or non Japanese Asian ethnicity.
• Any one parent or grandparent (maternal or paternal) is Japanese or non-Japanese Asian (e.g. China, Taiwan, Korea, Philippines, Thailand, Vietnam and Malaysia). Asian Indians are acceptable.
• Subjects who smoke more than 10 cigarettes or the equivalent in tobacco per day
• In the opinion of the investigator, any evidence of additional severe or uncontrolled systemic disease (eg, currently unstable or uncompensated hepatic, cardiovascular, or respiratory disease) or laboratory finding, physical examination, hematology, clinical chemistry, urinalysis, vital signs, or 12-lead ECG that makes it undesirable for the subject to participate in the study.
• Subjects with an active renal transplant (subjects who have previously received a renal transplant and are currently undergoing dialysis due to transplant failure may be enrolled).
• Acute coronary syndrome within 6 months prior to administration of the investigational product.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Orlando, Florida, United States

Location

Related Links

• CSR\_Synopsis\_D1532C00081.pdf

MeSH Terms

Conditions

Renal Insufficiency

Interventions

AZD 6244

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Thomas C Marbury, MD

  Orlando Clinical Research Centre, US

  PRINCIPAL INVESTIGATOR

• Ian Smith, MD

  Astrazeneca United kingdom

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2014
• First Posted: February 14, 2014
• Study Start: March 1, 2014
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: June 30, 2015

Record last verified: 2015-06

Locations

US (1)