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Investigate the Safety and Tolerability of AZD6244 Monotherapy or + Docetaxel in Japanese Patients With Advanced Solid Malignancies or Non-Small Cell Lung Cancer

Sponsor
AstraZeneca (Industry)
Overall Status
Completed
CT.gov ID
NCT01605916
Collaborator
(none)
33
Enrollment
3
Locations
5
Arms
35
Duration (Months)
11
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The objective of this study will be to investigate the safety and tolerability of AZD6244 given monotherapy or in combination with docetaxel as 2nd line therapy in Japanese patients with Advanced Solid Malignancies or Locally Advanced or Metastatic Non-Small Cell Lung Cancer. In addition, the pharmacokinetic profile of AZD6244 will be investigated. Following the combination regimen dose escalation phase (Part A) of the study additional patients may be enrolled to a dose expansion phase (Part B) to refine further the safety, tolerability, pharmacokinetics and biological activity of the combination in this patient population.

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed Description

The objective of the combination therapy part of this study will be to investigate the safety and tolerability of AZD6244 given in combination with docetaxel as 2nd line therapy in Japanese patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer (Stage IIIB-IV). In addition, the pharmacokinetic profile of AZD6244 and docetaxel will be investigated.

The objective of the monotherapy part of this study will be to investigate the safety and tolerability of AZD6244 given as a monotherapy in Japanese patients with advanced solid malignancies. In addition, the pharmacokinetic profile of monotherapy AZD6244 will be investigated.

Study Design

Study Type:
Interventional
Actual Enrollment :
33 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I, Open-Label Study to Investigate the Safety and Tolerability of AZD6244 (Selumetinib) When Given as a Monotherapy in Japanese Patients With Advanced Solid Malignancies, and When Given in Combination With Docetaxel as 2nd Line Therapy in Japanese Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (Stage IIIB-IV)
Study Start Date :
Jun 1, 2012
Actual Primary Completion Date :
Apr 1, 2015
Actual Study Completion Date :
May 1, 2015

Arms and Interventions

Arm Intervention/Treatment
Experimental: Selumetinib (AZD6244) 25 mg

monotherapy

Drug: AZD6244
Tablet Oral bid
Other Names:
  • Selumetinib (AZD6244)

    		•
    Experimental: Selumetinib (AZD6244) 50 mg

    monotherapy

    Drug: AZD6244
    Tablet Oral bid
    Other Names:
  • Selumetinib (AZD6244)

    		•
    Experimental: Selumetinib (AZD6244) 75 mg

    monotherapy

    Drug: AZD6244
    Tablet Oral bid
    Other Names:
  • Selumetinib (AZD6244)

    		•
    Experimental: Selumetinib (AZD6244) 75 mg + Doce

    Combination

    Drug: AZD6244
    Tablet Oral bid
    Other Names:
  • Selumetinib (AZD6244)

    		•
    Experimental: Selumetinib (AZD6244) 25 mg + Doce

    combination

    Drug: AZD6244
    Tablet Oral bid
    Other Names:
  • Selumetinib (AZD6244)

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Cmax of Selumetinib After Single Dose [Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72 hours post-dose]

      Pharmacokinetic parameter (Cmax: maximum plasma concentration) of Selumetinib following single oral dose of Selumetinib

    2. Tmax of Selumetinib After Single Dose [Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72 hours post-dose]

      Pharmacokinetic parameter (tmax: time to reach the maximum plasma concentration) of Selumetinib following single oral dose of Selumetinib

    3. AUC(0-12) of Selumetinib After Single Dose [Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose]

      Pharmacokinetic parameter (AUC(0-12): area under the plasma concentration-time curve from zero to 12 hours post-dosey) of Selumetinib following single oral dose of Selumetinib

    4. Cmax of N-desmethyl Selumetinib After Single Dose [Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72 hours post-dose]

      Pharmacokinetic parameter (Cmax: maximum plasma concentration) of N-desmethyl Selumetinib following single oral dose of Selumetinib

    5. Tmax of N-desmethyl Selumetinib After Single Dose [Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72 hours post-dose]

      Pharmacokinetic parameter (tmax: time to reach the maximum plasma concentration) of N-desmethyl Selumetinib following single oral dose of Selumetinib

    6. AUC(0-12) of N-desmethyl Selumetinib After Single Dose [Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose]

      Pharmacokinetic parameter (AUC(0-12): area under the plasma concentration-time curve from zero to 12 hours post-dose) of N-desmethyl Selumetinib following single oral dose of Selumetinib

    7. Cmax of Selumetinib During Oral Twice Daily Dose of Selumetinib [Day 8: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose]

      Pharmacokinetic parameter (Cmax: maximum plasma concentration) of Selumetinib during oral twice daily dose of Selumetinib

    8. Tmax of Selumetinib During Oral Twice Daily Dose of Selumetinib [Day 8: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose]

      Pharmacokinetic parameter (tmax: time to reach the maximum plasma concentration) of Selumetinib during oral twice daily dose of Selumetinib

    9. AUC(0-12) of Selumetinib During Oral Twice Daily Dose of Selumetinib [Day 8: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose]

      Pharmacokinetic parameter (AUC(0-12): area under the plasma concentration-time curve from zero to 12 hours post-dose) of Selumetinib during oral twice daily dose of Selumetinib

    10. Cmax of N-desmethyl Selumetinib During Oral Twice Daily Dose of Selumetinib [Day 8: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose]

      Pharmacokinetic parameter (Cmax: maximum plasma concentration) of N-desmethyl Selumetinib during oral twice daily dose of Selumetinib

    11. Tmax of N-desmethyl Selumetinib During Oral Twice Daily Dose of Selumetinib [Day 8: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose]

      Pharmacokinetic parameter (tmax: time to reach the maximum plasma concentration) of N-desmethyl Selumetinib during oral twice daily dose of Selumetinib

    12. AUC(0-12) of N-desmethyl Selumetinib During Oral Twice Daily Dose of Selumetinib [Day 8: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose]

      Pharmacokinetic parameter (AUC(0-12): area under the plasma concentration-time curve from zero to 12 hours post-dose) of N-desmethyl Selumetinib during oral twice daily dose of Selumetinib

    Secondary Outcome Measures

    1. Cmax of Docetaxel Following Intravenous Infusion of Docetaxel 60 mg/m2 [Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose]

      Pharmacokinetic parameter (Cmax: maximum plasma concentration) of docetaxel following intravenous infusion of docetaxel 60 mg/m2 in combination with Selumetinib

    2. Tmax of Docetaxel Following Intravenous Infusion of Docetaxel 60 mg/m2 [Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose]

      Pharmacokinetic parameter (tmax: time to reach the maximum plasma concentration) of docetaxel following intravenous infusion of docetaxel 60 mg/m2 in combination with Selumetinib

    3. AUC(0-12) of Docetaxel Following Intravenous Infusion of Docetaxel 60 mg/m2 [Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose]

      Pharmacokinetic parameter (AUC(0-12): area under the plasma concentration-time curve from zero to 12 hours post-dose) of docetaxel following intravenous infusion of docetaxel 60 mg/m2 in combination with Selumetinib

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    20 Years to 130 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Patients diagnosed with lung cancer who have not responded to prior therapy or have become worse.

    • Patients who have overall good general conditions.

    • Patients who have at least one lesion that can be accurately assessed by imaging.

    • Patients who have appropriate renal conditions confirmed by test results for taking part in the study.

    • Evidence of non-childbearing status for women of childbearing potential, or postmenopausal status.

    Exclusion Criteria:

    • Patients with brain metastases or spinal cord compression.

    • Patients with significant abnormal ECG findings.

    • Patients with evidence of severe or uncontrolled systemic disease.

    • The main organ functional test values for bone marrow, kidney, and liver, etc., do not meet the standards.

    • Patients with known hypersensitivity to docetaxel or products containing polysorbate

    Only for monotherapy cohort eligibility criteria Patients with advanced solid malignancies refractory to standard treatment or for which no standard therapy exists irrespective of the stage and previous treatment.

    Patients with histologically or cytologically confirmed advanced solid malignancies.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Fukuoka-shi Japan
    2 Research Site Kashiwa-shi Japan
    3 Research Site Nagoya-shi Japan

    Sponsors and Collaborators

    • AstraZeneca

    Investigators

    • Study Director: Ian Smith, Medical Science Director, AstraZeneca
    • Principal Investigator: Yuichiro Ohe, Medical Doctor, National Cancer Centre East
    • Principal Investigator: Hideo Saka, Medical Doctor, National Hospital Organisation Nagoya Medical Centre
    • Principal Investigator: Takashi Seto, Medical Doctor, National Hospital Organization Kyushu Cancer Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT01605916
    Other Study ID Numbers:
    • D1532C00067
    First Posted:
    May 25, 2012
    Last Update Posted:
    Oct 21, 2016
    Last Verified:
    Sep 1, 2016
    Keywords provided by AstraZeneca
    Cancer,
    Tumour,
    Metastatic,
    Lung cancer,
    Non-Small Cell Lung Cancer
    Additional relevant MeSH terms:
    Lung Neoplasms
    Carcinoma, Non-Small-Cell Lung
    Neoplasms

    Study Results

    Participant Flow

    Recruitment Details First patient enrolled on 01 June 2012. Last subject last visit on 30 March 2015.
    Pre-assignment Detail Out of 33 enrolled subjects, 25 subjects were assigned to selumetinib (AZD6244, ARRY-142886), and 8 subjects were not assigned. The reasons of no assignment were 'Screen failure' (7 subjects) and 'Withdrawal by subject' (1 subject).
    Arm/Group Title Combination Therapy Cohort 1 Selumetinib 75 mg + Doce Combination Therapy Cohort 2 Selumetinib 25 mg + Doce Monotherapy Cohort 1 Selumetinib 25 mg Monotherapy Cohort 2 Selumetinib 50 mg Monotherapy Cohort 3 Selumetinib 75 mg
    Arm/Group Description Combination therapy of Selumetinib 75 mg twice a day with docetaxel 60 mg/m2 every 21 days for Japanese patients with locally advanced or metastatic non-small cell lung cancer Combination therapy of Selumetinib 25 mg twice a day with docetaxel 60 mg/m2 every 21 days for Japanese patients with locally advanced or metastatic non-small cell lung cancer Monotherapy of Selumetinib 25 mg twice a day for Japanese patients with advanced solid malignancies Monotherapy of Selumetinib 50 mg twice a day for Japanese patients with advanced solid malignancies Monotherapy of Selumetinib 75 mg twice a day for Japanese patients with advanced solid malignancies
    Period Title: Overall Study
    STARTED 4 4 4 6 7
    COMPLETED 0 0 1 0 1
    NOT COMPLETED 4 4 3 6 6

    Baseline Characteristics

    Arm/Group Title Combination Therapy Cohort 1 Selumetinib 75 mg + Doce Combination Therapy Cohort 2 Selumetinib 25 mg + Doce Monotherapy Cohort 1 Selumetinib 25 mg Monotherapy Cohort 2 Selumetinib 50 mg Monotherapy Cohort 3 Selumetinib 75 mg Total
    Arm/Group Description Combination therapy of Selumetinib 75 mg twice a day with docetaxel 60 mg/m2 every 21 days for Japanese patients with locally advanced or metastatic non-small cell lung cancer Combination therapy of Selumetinib 25 mg twice a day with docetaxel 60 mg/m2 every 21 days for Japanese patients with locally advanced or metastatic non-small cell lung cancer Monotherapy of Selumetinib 25 mg twice a day for Japanese patients with advanced solid malignancies Monotherapy of Selumetinib 50 mg twice a day for Japanese patients with advanced solid malignancies Monotherapy of Selumetinib 75 mg twice a day for Japanese patients with advanced solid malignancies Total of all reporting groups
    Overall Participants 4 4 4 6 7 25
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    55.5
    (17.33)
    58.8
    (8.50)
    60.0
    (12.36)
    60.0
    (11.75)
    66.7
    (12.22)
    61.0
    (12.15)
    Sex: Female, Male (Count of Participants)
    Female
    1
    25%
    1
    25%
    2
    50%
    1
    16.7%
    4
    57.1%
    9
    36%
    Male
    3
    75%
    3
    75%
    2
    50%
    5
    83.3%
    3
    42.9%
    16
    64%

    Outcome Measures

    1. Primary Outcome
    Title Cmax of Selumetinib After Single Dose
    Description Pharmacokinetic parameter (Cmax: maximum plasma concentration) of Selumetinib following single oral dose of Selumetinib
    Time Frame Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Analysis Set
    Arm/Group Title Combination Therapy Cohort 1 Selumetinib 75 mg + Doce Combination Therapy Cohort 2 Selumetinib 25 mg + Doce Monotherapy Cohort 1 Selumetinib 25 mg Monotherapy Cohort 2 Selumetinib 50 mg Monotherapy Cohort 3 Selumetinib 75 mg
    Arm/Group Description Combination therapy of Selumetinib 75 mg twice a day with docetaxel 60 mg/m2 every 21 days for Japanese patients with locally advanced or metastatic non-small cell lung cancer Combination therapy of Selumetinib 25 mg twice a day with docetaxel 60 mg/m2 every 21 days for Japanese patients with locally advanced or metastatic non-small cell lung cancer Monotherapy of Selumetinib 25 mg twice a day for Japanese patients with advanced solid malignancies Monotherapy of Selumetinib 50 mg twice a day for Japanese patients with advanced solid malignancies Monotherapy of Selumetinib 75 mg twice a day for Japanese patients with advanced solid malignancies
    Measure Participants 4 4 4 6 7
    Geometric Mean (Geometric Coefficient of Variation) [ng/mL]
    2534
    (40.45)
    1073
    (35.18)
    370.3
    (96.87)
    897.1
    (69.34)
    2084
    (50.85)
    2. Primary Outcome
    Title Tmax of Selumetinib After Single Dose
    Description Pharmacokinetic parameter (tmax: time to reach the maximum plasma concentration) of Selumetinib following single oral dose of Selumetinib
    Time Frame Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Analysis Set
    Arm/Group Title Combination Therapy Cohort 1 Selumetinib 75 mg + Doce Combination Therapy Cohort 2 Selumetinib 25 mg + Doce Monotherapy Cohort 1 Selumetinib 25 mg Monotherapy Cohort 2 Selumetinib 50 mg Monotherapy Cohort 3 Selumetinib 75 mg
    Arm/Group Description Combination therapy of Selumetinib 75 mg twice a day with docetaxel 60 mg/m2 every 21 days for Japanese patients with locally advanced or metastatic non-small cell lung cancer Combination therapy of Selumetinib 25 mg twice a day with docetaxel 60 mg/m2 every 21 days for Japanese patients with locally advanced or metastatic non-small cell lung cancer Monotherapy of Selumetinib 25 mg twice a day for Japanese patients with advanced solid malignancies Monotherapy of Selumetinib 50 mg twice a day for Japanese patients with advanced solid malignancies Monotherapy of Selumetinib 75 mg twice a day for Japanese patients with advanced solid malignancies
    Measure Participants 4 4 4 6 7
    Median (Full Range) [hour]
    1.49
    (40.45)
    1.00
    (35.18)
    1.74
    1.51
    0.98
    3. Primary Outcome
    Title AUC(0-12) of Selumetinib After Single Dose
    Description Pharmacokinetic parameter (AUC(0-12): area under the plasma concentration-time curve from zero to 12 hours post-dosey) of Selumetinib following single oral dose of Selumetinib
    Time Frame Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Analysis Set
    Arm/Group Title Combination Therapy Cohort 1 Selumetinib 75 mg + Doce Combination Therapy Cohort 2 Selumetinib 25 mg + Doce Monotherapy Cohort 1 Selumetinib 25 mg Monotherapy Cohort 2 Selumetinib 50 mg Monotherapy Cohort 3 Selumetinib 75 mg
    Arm/Group Description Combination therapy of Selumetinib 75 mg twice a day with docetaxel 60 mg/m2 every 21 days for Japanese patients with locally advanced or metastatic non-small cell lung cancer Combination therapy of Selumetinib 25 mg twice a day with docetaxel 60 mg/m2 every 21 days for Japanese patients with locally advanced or metastatic non-small cell lung cancer Monotherapy of Selumetinib 25 mg twice a day for Japanese patients with advanced solid malignancies Monotherapy of Selumetinib 50 mg twice a day for Japanese patients with advanced solid malignancies Monotherapy of Selumetinib 75 mg twice a day for Japanese patients with advanced solid malignancies
    Measure Participants 4 4 4 6 7
    Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL]
    6784
    (26.63)
    1599
    (35.48)
    1021
    (30.62)
    2723
    (33.24)
    5578
    (35.77)
    4. Primary Outcome
    Title Cmax of N-desmethyl Selumetinib After Single Dose
    Description Pharmacokinetic parameter (Cmax: maximum plasma concentration) of N-desmethyl Selumetinib following single oral dose of Selumetinib
    Time Frame Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Analysis Set
    Arm/Group Title Combination Therapy Cohort 1 Selumetinib 75 mg + Doce Combination Therapy Cohort 2 Selumetinib 25 mg + Doce Monotherapy Cohort 1 Selumetinib 25 mg Monotherapy Cohort 2 Selumetinib 50 mg Monotherapy Cohort 3 Selumetinib 75 mg
    Arm/Group Description Combination therapy of Selumetinib 75 mg twice a day with docetaxel 60 mg/m2 every 21 days for Japanese patients with locally advanced or metastatic non-small cell lung cancer Combination therapy of Selumetinib 25 mg twice a day with docetaxel 60 mg/m2 every 21 days for Japanese patients with locally advanced or metastatic non-small cell lung cancer Monotherapy of Selumetinib 25 mg twice a day for Japanese patients with advanced solid malignancies Monotherapy of Selumetinib 50 mg twice a day for Japanese patients with advanced solid malignancies Monotherapy of Selumetinib 75 mg twice a day for Japanese patients with advanced solid malignancies
    Measure Participants 4 4 4 6 7
    Geometric Mean (Geometric Coefficient of Variation) [ng/mL]
    130.8
    (63.44)
    68.61
    (15.10)
    27.50
    (41.42)
    46.55
    (57.74)
    136.6
    (29.28)
    5. Primary Outcome
    Title Tmax of N-desmethyl Selumetinib After Single Dose
    Description Pharmacokinetic parameter (tmax: time to reach the maximum plasma concentration) of N-desmethyl Selumetinib following single oral dose of Selumetinib
    Time Frame Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Analysis Set
    Arm/Group Title Combination Therapy Cohort 1 Selumetinib 75 mg + Doce Combination Therapy Cohort 2 Selumetinib 25 mg + Doce Monotherapy Cohort 1 Selumetinib 25 mg Monotherapy Cohort 2 Selumetinib 50 mg Monotherapy Cohort 3 Selumetinib 75 mg
    Arm/Group Description Combination therapy of Selumetinib 75 mg twice a day with docetaxel 60 mg/m2 every 21 days for Japanese patients with locally advanced or metastatic non-small cell lung cancer Combination therapy of Selumetinib 25 mg twice a day with docetaxel 60 mg/m2 every 21 days for Japanese patients with locally advanced or metastatic non-small cell lung cancer Monotherapy of Selumetinib 25 mg twice a day for Japanese patients with advanced solid malignancies Monotherapy of Selumetinib 50 mg twice a day for Japanese patients with advanced solid malignancies Monotherapy of Selumetinib 75 mg twice a day for Japanese patients with advanced solid malignancies
    Measure Participants 4 4 4 6 7
    Median (Full Range) [hour]
    1.75
    (40.45)
    1.00
    (35.18)
    1.74
    1.75
    1.47
    6. Primary Outcome
    Title AUC(0-12) of N-desmethyl Selumetinib After Single Dose
    Description Pharmacokinetic parameter (AUC(0-12): area under the plasma concentration-time curve from zero to 12 hours post-dose) of N-desmethyl Selumetinib following single oral dose of Selumetinib
    Time Frame Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Analysis Set
    Arm/Group Title Combination Therapy Cohort 1 Selumetinib 75 mg + Doce Combination Therapy Cohort 2 Selumetinib 25 mg + Doce Monotherapy Cohort 1 Selumetinib 25 mg Monotherapy Cohort 2 Selumetinib 50 mg Monotherapy Cohort 3 Selumetinib 75 mg
    Arm/Group Description Combination therapy of Selumetinib 75 mg twice a day with docetaxel 60 mg/m2 every 21 days for Japanese patients with locally advanced or metastatic non-small cell lung cancer Combination therapy of Selumetinib 25 mg twice a day with docetaxel 60 mg/m2 every 21 days for Japanese patients with locally advanced or metastatic non-small cell lung cancer Monotherapy of Selumetinib 25 mg twice a day for Japanese patients with advanced solid malignancies Monotherapy of Selumetinib 50 mg twice a day for Japanese patients with advanced solid malignancies Monotherapy of Selumetinib 75 mg twice a day for Japanese patients with advanced solid malignancies
    Measure Participants 4 4 4 6 7
    Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL]
    409.6
    (32.29)
    159.6
    (33.22)
    88.79
    (7.700)
    182.6
    (48.45)
    495.4
    (17.99)
    7. Primary Outcome
    Title Cmax of Selumetinib During Oral Twice Daily Dose of Selumetinib
    Description Pharmacokinetic parameter (Cmax: maximum plasma concentration) of Selumetinib during oral twice daily dose of Selumetinib
    Time Frame Day 8: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Analysis Set
    Arm/Group Title Combination Therapy Cohort 1 Selumetinib 75 mg + Doce Combination Therapy Cohort 2 Selumetinib 25 mg + Doce Monotherapy Cohort 1 Selumetinib 25 mg Monotherapy Cohort 2 Selumetinib 50 mg Monotherapy Cohort 3 Selumetinib 75 mg
    Arm/Group Description Combination therapy of Selumetinib 75 mg twice a day with docetaxel 60 mg/m2 every 21 days for Japanese patients with locally advanced or metastatic non-small cell lung cancer Combination therapy of Selumetinib 25 mg twice a day with docetaxel 60 mg/m2 every 21 days for Japanese patients with locally advanced or metastatic non-small cell lung cancer Monotherapy of Selumetinib 25 mg twice a day for Japanese patients with advanced solid malignancies Monotherapy of Selumetinib 50 mg twice a day for Japanese patients with advanced solid malignancies Monotherapy of Selumetinib 75 mg twice a day for Japanese patients with advanced solid malignancies
    Measure Participants 3 4 4 6 6
    Geometric Mean (Geometric Coefficient of Variation) [ng/mL]
    2437
    (64.93)
    662.3
    (31.07)
    623.4
    (46.09)
    1012
    (47.08)
    2178
    (79.67)
    8. Primary Outcome
    Title Tmax of Selumetinib During Oral Twice Daily Dose of Selumetinib
    Description Pharmacokinetic parameter (tmax: time to reach the maximum plasma concentration) of Selumetinib during oral twice daily dose of Selumetinib
    Time Frame Day 8: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Analysis Set
    Arm/Group Title Combination Therapy Cohort 1 Selumetinib 75 mg + Doce Combination Therapy Cohort 2 Selumetinib 25 mg + Doce Monotherapy Cohort 1 Selumetinib 25 mg Monotherapy Cohort 2 Selumetinib 50 mg Monotherapy Cohort 3 Selumetinib 75 mg
    Arm/Group Description Combination therapy of Selumetinib 75 mg twice a day with docetaxel 60 mg/m2 every 21 days for Japanese patients with locally advanced or metastatic non-small cell lung cancer Combination therapy of Selumetinib 25 mg twice a day with docetaxel 60 mg/m2 every 21 days for Japanese patients with locally advanced or metastatic non-small cell lung cancer Monotherapy of Selumetinib 25 mg twice a day for Japanese patients with advanced solid malignancies Monotherapy of Selumetinib 50 mg twice a day for Japanese patients with advanced solid malignancies Monotherapy of Selumetinib 75 mg twice a day for Japanese patients with advanced solid malignancies
    Measure Participants 3 4 4 6 6
    Median (Full Range) [hour]
    3.97
    (40.45)
    1.25
    (35.18)
    1.23
    1.96
    1.50
    9. Primary Outcome
    Title AUC(0-12) of Selumetinib During Oral Twice Daily Dose of Selumetinib
    Description Pharmacokinetic parameter (AUC(0-12): area under the plasma concentration-time curve from zero to 12 hours post-dose) of Selumetinib during oral twice daily dose of Selumetinib
    Time Frame Day 8: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Analysis Set
    Arm/Group Title Combination Therapy Cohort 1 Selumetinib 75 mg + Doce Combination Therapy Cohort 2 Selumetinib 25 mg + Doce Monotherapy Cohort 1 Selumetinib 25 mg Monotherapy Cohort 2 Selumetinib 50 mg Monotherapy Cohort 3 Selumetinib 75 mg
    Arm/Group Description Combination therapy of Selumetinib 75 mg twice a day with docetaxel 60 mg/m2 every 21 days for Japanese patients with locally advanced or metastatic non-small cell lung cancer Combination therapy of Selumetinib 25 mg twice a day with docetaxel 60 mg/m2 every 21 days for Japanese patients with locally advanced or metastatic non-small cell lung cancer Monotherapy of Selumetinib 25 mg twice a day for Japanese patients with advanced solid malignancies Monotherapy of Selumetinib 50 mg twice a day for Japanese patients with advanced solid malignancies Monotherapy of Selumetinib 75 mg twice a day for Japanese patients with advanced solid malignancies
    Measure Participants 3 4 4 6 6
    Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL]
    13050
    (12.86)
    2334
    (42.31)
    2130
    (20.09)
    4818
    (20.07)
    8734
    (55.99)
    10. Primary Outcome
    Title Cmax of N-desmethyl Selumetinib During Oral Twice Daily Dose of Selumetinib
    Description Pharmacokinetic parameter (Cmax: maximum plasma concentration) of N-desmethyl Selumetinib during oral twice daily dose of Selumetinib
    Time Frame Day 8: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Analysis Set
    Arm/Group Title Combination Therapy Cohort 1 Selumetinib 75 mg + Doce Combination Therapy Cohort 2 Selumetinib 25 mg + Doce Monotherapy Cohort 1 Selumetinib 25 mg Monotherapy Cohort 2 Selumetinib 50 mg Monotherapy Cohort 3 Selumetinib 75 mg
    Arm/Group Description Combination therapy of Selumetinib 75 mg twice a day with docetaxel 60 mg/m2 every 21 days for Japanese patients with locally advanced or metastatic non-small cell lung cancer Combination therapy of Selumetinib 25 mg twice a day with docetaxel 60 mg/m2 every 21 days for Japanese patients with locally advanced or metastatic non-small cell lung cancer Monotherapy of Selumetinib 25 mg twice a day for Japanese patients with advanced solid malignancies Monotherapy of Selumetinib 50 mg twice a day for Japanese patients with advanced solid malignancies Monotherapy of Selumetinib 75 mg twice a day for Japanese patients with advanced solid malignancies
    Measure Participants 3 4 4 6 6
    Geometric Mean (Geometric Coefficient of Variation) [ng/mL]
    38.91
    (133.7)
    34.46
    (35.21)
    36.16
    (31.26)
    42.18
    (56.89)
    84.56
    (74.73)
    11. Primary Outcome
    Title Tmax of N-desmethyl Selumetinib During Oral Twice Daily Dose of Selumetinib
    Description Pharmacokinetic parameter (tmax: time to reach the maximum plasma concentration) of N-desmethyl Selumetinib during oral twice daily dose of Selumetinib
    Time Frame Day 8: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Analysis Set
    Arm/Group Title Combination Therapy Cohort 1 Selumetinib 75 mg + Doce Combination Therapy Cohort 2 Selumetinib 25 mg + Doce Monotherapy Cohort 1 Selumetinib 25 mg Monotherapy Cohort 2 Selumetinib 50 mg Monotherapy Cohort 3 Selumetinib 75 mg
    Arm/Group Description Combination therapy of Selumetinib 75 mg twice a day with docetaxel 60 mg/m2 every 21 days for Japanese patients with locally advanced or metastatic non-small cell lung cancer Combination therapy of Selumetinib 25 mg twice a day with docetaxel 60 mg/m2 every 21 days for Japanese patients with locally advanced or metastatic non-small cell lung cancer Monotherapy of Selumetinib 25 mg twice a day for Japanese patients with advanced solid malignancies Monotherapy of Selumetinib 50 mg twice a day for Japanese patients with advanced solid malignancies Monotherapy of Selumetinib 50 mg twice a day for Japanese patients with advanced solid malignancies
    Measure Participants 3 4 4 6 6
    Median (Full Range) [hour]
    3.97
    (40.45)
    1.25
    (35.18)
    1.25
    1.96
    1.74
    12. Primary Outcome
    Title AUC(0-12) of N-desmethyl Selumetinib During Oral Twice Daily Dose of Selumetinib
    Description Pharmacokinetic parameter (AUC(0-12): area under the plasma concentration-time curve from zero to 12 hours post-dose) of N-desmethyl Selumetinib during oral twice daily dose of Selumetinib
    Time Frame Day 8: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Analysis Set
    Arm/Group Title Combination Therapy Cohort 1 Selumetinib 75 mg + Doce Combination Therapy Cohort 2 Selumetinib 25 mg + Doce Monotherapy Cohort 1 Selumetinib 25 mg Monotherapy Cohort 2 Selumetinib 50 mg Monotherapy Cohort 3 Selumetinib 75 mg
    Arm/Group Description Combination therapy of Selumetinib 75 mg twice a day with docetaxel 60 mg/m2 every 21 days for Japanese patients with locally advanced or metastatic non-small cell lung cancer Combination therapy of Selumetinib 25 mg twice a day with docetaxel 60 mg/m2 every 21 days for Japanese patients with locally advanced or metastatic non-small cell lung cancer Monotherapy of Selumetinib 25 mg twice a day for Japanese patients with advanced solid malignancies Monotherapy of Selumetinib 50 mg twice a day for Japanese patients with advanced solid malignancies Monotherapy of Selumetinib 50 mg twice a day for Japanese patients with advanced solid malignancies
    Measure Participants 3 4 4 6 6
    Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL]
    241.5
    (115.7)
    150.4
    (44.08)
    146.3
    (29.77)
    251.3
    (39.33)
    445.0
    (61.88)
    13. Secondary Outcome
    Title Cmax of Docetaxel Following Intravenous Infusion of Docetaxel 60 mg/m2
    Description Pharmacokinetic parameter (Cmax: maximum plasma concentration) of docetaxel following intravenous infusion of docetaxel 60 mg/m2 in combination with Selumetinib
    Time Frame Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Analysis Set
    Arm/Group Title Combination Therapy Cohort 1 Selumetinib 75 mg + Doce Combination Therapy Cohort 2 Selumetinib 25 mg + Doce
    Arm/Group Description Combination therapy of Selumetinib 75 mg twice a day with docetaxel 60 mg/m2 every 21 days for Japanese patients with locally advanced or metastatic non-small cell lung cancer Combination therapy of Selumetinib 25 mg twice a day with docetaxel 60 mg/m2 every 21 days for Japanese patients with locally advanced or metastatic non-small cell lung cancer
    Measure Participants 4 4
    Geometric Mean (Geometric Coefficient of Variation) [ng/mL]
    2329
    (9.805)
    2726
    (27.92)
    14. Secondary Outcome
    Title Tmax of Docetaxel Following Intravenous Infusion of Docetaxel 60 mg/m2
    Description Pharmacokinetic parameter (tmax: time to reach the maximum plasma concentration) of docetaxel following intravenous infusion of docetaxel 60 mg/m2 in combination with Selumetinib
    Time Frame Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Analysis Set
    Arm/Group Title Combination Therapy Cohort 1 Selumetinib 75 mg + Doce Combination Therapy Cohort 2 Selumetinib 25 mg + Doce
    Arm/Group Description Combination therapy of Selumetinib 75 mg twice a day with docetaxel 60 mg/m2 every 21 days for Japanese patients with locally advanced or metastatic non-small cell lung cancer Combination therapy of Selumetinib 25 mg twice a day with docetaxel 60 mg/m2 every 21 days for Japanese patients with locally advanced or metastatic non-small cell lung cancer
    Measure Participants 4 4
    Median (Full Range) [hour]
    0.99
    (9.805)
    0.99
    (27.92)
    15. Secondary Outcome
    Title AUC(0-12) of Docetaxel Following Intravenous Infusion of Docetaxel 60 mg/m2
    Description Pharmacokinetic parameter (AUC(0-12): area under the plasma concentration-time curve from zero to 12 hours post-dose) of docetaxel following intravenous infusion of docetaxel 60 mg/m2 in combination with Selumetinib
    Time Frame Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Analysis Set
    Arm/Group Title Combination Therapy Cohort 1 Selumetinib 75 mg + Doce Combination Therapy Cohort 2 Selumetinib 25 mg + Doce
    Arm/Group Description Combination therapy of Selumetinib 75 mg twice a day with docetaxel 60 mg/m2 every 21 days for Japanese patients with locally advanced or metastatic non-small cell lung cancer Combination therapy of Selumetinib 25 mg twice a day with docetaxel 60 mg/m2 every 21 days for Japanese patients with locally advanced or metastatic non-small cell lung cancer
    Measure Participants 4 4
    Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL]
    2422
    (13.72)
    3056
    (28.64)

    Adverse Events

    Time Frame Adverse events were collected throughout the study, from informed consent until the end of the followup period. The follow-up period is defined as 28 days after investigational prooduct and/or docetaxel is discontinued.
    Adverse Event Reporting Description
    Arm/Group Title Combination Therapy Cohort 1 Selumetinib 75 mg + Doce Combination Therapy Cohort 2 Selumetinib 25 mg + Doce Monotherapy Cohort 1 Selumetinib 25 mg Monotherapy Cohort 2 Selumetinib 50 mg Monotherapy Cohort 3 Selumetinib 75 mg
    Arm/Group Description Combination therapy of Selumetinib 75 mg twice a day with docetaxel 60 mg/m2 every 21 days for Japanese patients with locally advanced or metastatic non-small cell lung cancer Combination therapy of Selumetinib 25 mg twice a day with docetaxel 60 mg/m2 every 21 days for Japanese patients with locally advanced or metastatic non-small cell lung cancer Monotherapy of Selumetinib 25 mg twice a day for Japanese patients with advanced solid malignancies Monotherapy of Selumetinib 50 mg twice a day for Japanese patients with advanced solid malignancies Monotherapy of Selumetinib 75 mg twice a day for Japanese patients with advanced solid malignancies
    All Cause Mortality
    Combination Therapy Cohort 1 Selumetinib 75 mg + Doce Combination Therapy Cohort 2 Selumetinib 25 mg + Doce Monotherapy Cohort 1 Selumetinib 25 mg Monotherapy Cohort 2 Selumetinib 50 mg Monotherapy Cohort 3 Selumetinib 75 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Combination Therapy Cohort 1 Selumetinib 75 mg + Doce Combination Therapy Cohort 2 Selumetinib 25 mg + Doce Monotherapy Cohort 1 Selumetinib 25 mg Monotherapy Cohort 2 Selumetinib 50 mg Monotherapy Cohort 3 Selumetinib 75 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/4 (0%) 0/4 (0%) 1/4 (25%) 1/6 (16.7%) 2/7 (28.6%)
    Gastrointestinal disorders
    Enterocolitis 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1
    Infections and infestations
    Pneumonia bacterial 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1
    Injury, poisoning and procedural complications
    Humerus fracture 0/4 (0%) 0 0/4 (0%) 0 1/4 (25%) 1 0/6 (0%) 0 0/7 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Interstitial lung disease 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1
    Pneumonitis 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0
    Other (Not Including Serious) Adverse Events
    Combination Therapy Cohort 1 Selumetinib 75 mg + Doce Combination Therapy Cohort 2 Selumetinib 25 mg + Doce Monotherapy Cohort 1 Selumetinib 25 mg Monotherapy Cohort 2 Selumetinib 50 mg Monotherapy Cohort 3 Selumetinib 75 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/4 (100%) 4/4 (100%) 4/4 (100%) 6/6 (100%) 7/7 (100%)
    Blood and lymphatic system disorders
    Anaemia 1/4 (25%) 3/4 (75%) 0/4 (0%) 0/6 (0%) 0/7 (0%)
    Febrile neutropenia 3/4 (75%) 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%)
    Leukopenia 0/4 (0%) 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%)
    Neutropenia 2/4 (50%) 2/4 (50%) 1/4 (25%) 1/6 (16.7%) 0/7 (0%)
    Cardiac disorders
    Bradycardia 1/4 (25%) 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%)
    Cardiac failure 0/4 (0%) 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%)
    Eye disorders
    Conjunctival haemorrhage 0/4 (0%) 0/4 (0%) 0/4 (0%) 0/6 (0%) 2/7 (28.6%)
    Eye oedema 0/4 (0%) 0/4 (0%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%)
    Retinal detachment 0/4 (0%) 0/4 (0%) 0/4 (0%) 2/6 (33.3%) 0/7 (0%)
    Visual impairment 1/4 (25%) 0/4 (0%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%)
    Xanthopsia 1/4 (25%) 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%)
    Gastrointestinal disorders
    Abdominal distension 0/4 (0%) 0/4 (0%) 1/4 (25%) 0/6 (0%) 0/7 (0%)
    Abdominal pain 0/4 (0%) 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%)
    Abdominal pain upper 0/4 (0%) 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%)
    Cheilitis 0/4 (0%) 2/4 (50%) 0/4 (0%) 0/6 (0%) 0/7 (0%)
    Constipation 0/4 (0%) 1/4 (25%) 1/4 (25%) 2/6 (33.3%) 2/7 (28.6%)
    Diarrhoea 2/4 (50%) 3/4 (75%) 1/4 (25%) 2/6 (33.3%) 5/7 (71.4%)
    Dry mouth 0/4 (0%) 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%)
    Gastritis 2/4 (50%) 1/4 (25%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%)
    Gastrooesophageal reflux disease 0/4 (0%) 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%)
    Haemorrhoids 0/4 (0%) 1/4 (25%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%)
    Nausea 2/4 (50%) 3/4 (75%) 0/4 (0%) 2/6 (33.3%) 2/7 (28.6%)
    Stomatitis 4/4 (100%) 1/4 (25%) 0/4 (0%) 1/6 (16.7%) 2/7 (28.6%)
    Toothache 1/4 (25%) 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%)
    Vomiting 3/4 (75%) 3/4 (75%) 1/4 (25%) 4/6 (66.7%) 2/7 (28.6%)
    General disorders
    Face oedema 1/4 (25%) 0/4 (0%) 0/4 (0%) 0/6 (0%) 2/7 (28.6%)
    Fatigue 0/4 (0%) 1/4 (25%) 0/4 (0%) 0/6 (0%) 2/7 (28.6%)
    Influenza like illness 0/4 (0%) 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%)
    Malaise 1/4 (25%) 2/4 (50%) 1/4 (25%) 3/6 (50%) 2/7 (28.6%)
    Non-cardiac chest pain 0/4 (0%) 0/4 (0%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%)
    Oedema 1/4 (25%) 1/4 (25%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%)
    Oedema peripheral 0/4 (0%) 0/4 (0%) 0/4 (0%) 0/6 (0%) 3/7 (42.9%)
    Pyrexia 0/4 (0%) 1/4 (25%) 0/4 (0%) 1/6 (16.7%) 1/7 (14.3%)
    Immune system disorders
    Food allergy 1/4 (25%) 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%)
    Infections and infestations
    Bronchitis 0/4 (0%) 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%)
    Conjunctivitis 0/4 (0%) 0/4 (0%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%)
    Cystitis 0/4 (0%) 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%)
    Herpes zoster 0/4 (0%) 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%)
    Infection 0/4 (0%) 0/4 (0%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%)
    Influenza 0/4 (0%) 0/4 (0%) 1/4 (25%) 0/6 (0%) 0/7 (0%)
    Nail infection 1/4 (25%) 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%)
    Nasopharyngitis 0/4 (0%) 0/4 (0%) 1/4 (25%) 0/6 (0%) 0/7 (0%)
    Paronychia 0/4 (0%) 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%)
    Pharyngitis 2/4 (50%) 1/4 (25%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%)
    Pneumonia 1/4 (25%) 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%)
    Respiratory tract infection 0/4 (0%) 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%)
    Upper respiratory tract infection 1/4 (25%) 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%)
    Injury, poisoning and procedural complications
    Fall 0/4 (0%) 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%)
    Investigations
    Alanine aminotransferase increased 3/4 (75%) 0/4 (0%) 0/4 (0%) 1/6 (16.7%) 1/7 (14.3%)
    Aspartate aminotransferase increased 4/4 (100%) 1/4 (25%) 1/4 (25%) 2/6 (33.3%) 3/7 (42.9%)
    Blood alkaline phosphatase increased 2/4 (50%) 0/4 (0%) 1/4 (25%) 0/6 (0%) 0/7 (0%)
    Blood bilirubin increased 1/4 (25%) 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%)
    Blood creatinine increased 1/4 (25%) 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%)
    Blood urea increased 1/4 (25%) 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%)
    Gamma-glutamyltransferase increased 2/4 (50%) 1/4 (25%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%)
    Neutrophil count decreased 1/4 (25%) 3/4 (75%) 0/4 (0%) 0/6 (0%) 0/7 (0%)
    Platelet count decreased 1/4 (25%) 0/4 (0%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%)
    Weight decreased 0/4 (0%) 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%)
    White blood cell count decreased 2/4 (50%) 3/4 (75%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%)
    Metabolism and nutrition disorders
    Decreased appetite 2/4 (50%) 3/4 (75%) 0/4 (0%) 1/6 (16.7%) 2/7 (28.6%)
    Dehydration 1/4 (25%) 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%)
    Hyperglycaemia 1/4 (25%) 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%)
    Hypoalbuminaemia 0/4 (0%) 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 2/4 (50%) 0/4 (0%) 1/4 (25%) 0/6 (0%) 0/7 (0%)
    Arthritis 1/4 (25%) 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%)
    Back pain 0/4 (0%) 0/4 (0%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%)
    Chondrocalcinosis pyrophosphate 0/4 (0%) 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%)
    Myalgia 0/4 (0%) 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%)
    Neck pain 0/4 (0%) 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%)
    Nervous system disorders
    Dizziness 0/4 (0%) 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%)
    Headache 1/4 (25%) 0/4 (0%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%)
    Peripheral sensory neuropathy 1/4 (25%) 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%)
    Presyncope 1/4 (25%) 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%)
    Psychiatric disorders
    Delusion 1/4 (25%) 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%)
    Insomnia 1/4 (25%) 1/4 (25%) 1/4 (25%) 1/6 (16.7%) 1/7 (14.3%)
    Renal and urinary disorders
    Dysuria 0/4 (0%) 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%)
    Haematuria 0/4 (0%) 0/4 (0%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%)
    Respiratory, thoracic and mediastinal disorders
    Cough 0/4 (0%) 0/4 (0%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%)
    Epistaxis 1/4 (25%) 3/4 (75%) 0/4 (0%) 0/6 (0%) 0/7 (0%)
    Hiccups 1/4 (25%) 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%)
    Laryngeal pain 0/4 (0%) 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%)
    Oropharyngeal pain 3/4 (75%) 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%)
    Pharyngeal inflammation 0/4 (0%) 0/4 (0%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%)
    Skin and subcutaneous tissue disorders
    Alopecia 1/4 (25%) 2/4 (50%) 0/4 (0%) 0/6 (0%) 0/7 (0%)
    Dermatitis acneiform 2/4 (50%) 0/4 (0%) 2/4 (50%) 3/6 (50%) 4/7 (57.1%)
    Dry skin 1/4 (25%) 1/4 (25%) 0/4 (0%) 1/6 (16.7%) 2/7 (28.6%)
    Nail discolouration 1/4 (25%) 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%)
    Nail ridging 1/4 (25%) 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%)
    Onychomadesis 1/4 (25%) 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%)
    Pruritus 0/4 (0%) 0/4 (0%) 0/4 (0%) 1/6 (16.7%) 2/7 (28.6%)
    Rash 2/4 (50%) 0/4 (0%) 1/4 (25%) 0/6 (0%) 1/7 (14.3%)
    Rash maculo-papular 0/4 (0%) 2/4 (50%) 1/4 (25%) 1/6 (16.7%) 0/7 (0%)
    Skin irritation 0/4 (0%) 0/4 (0%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%)
    Vascular disorders
    Hypertension 1/4 (25%) 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%)
    Vascular pain 0/4 (0%) 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    All PIs were prohibited to disclose all information related to this study without AZ approval before this study was completed.

    Results Point of Contact

    Name/Title Masahiro Nii
    Organization Biometrics Department, Science Affairs Division, R&D, Astrazeneca Japan
    Phone
    Email Masahiro.Nii@astrazeneca.com
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT01605916
    Other Study ID Numbers:
    • D1532C00067
    First Posted:
    May 25, 2012
    Last Update Posted:
    Oct 21, 2016
    Last Verified:
    Sep 1, 2016