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A Dose-escalation Study of MK-8776 (SCH 900776) With and Without Gemcitabine in Participants With Solid Tumors or Lymphoma (MK-8776-002/P05248)

Sponsor
Merck Sharp & Dohme LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT00779584
Collaborator
(none)
45
Enrollment
9
Arms
31.3
Actual Duration (Months)

Study Details

Study Description

Brief Summary

This study of MK-8776 (SCH 900776) will evaluate its safety and tolerability when given as monotherapy or in combination with gemcitabine to participants with advanced solid tumors or lymphoma. Participants will be enrolled in cohorts that will receive sequentially higher doses of MK-8776 in combination with standard doses of gemcitabine The recommended combination doses for a Phase 2 trial (combination-RP2D) will be determined based on safety and biological activity. Up to 10 to 15 additional participants may be studied at the combination-RP2D.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
45 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1 Dose-Escalation Study of SCH 900776 as Monotherapy and in Combination With Gemcitabine in Subjects With Advanced Solid Tumors or Lymphoma
Actual Study Start Date :
Oct 17, 2008
Actual Primary Completion Date :
May 28, 2011
Actual Study Completion Date :
May 28, 2011

Arms and Interventions

Arm Intervention/Treatment
Experimental: MK-8776 10mg/m^2+Gemcitabine 800mg/m^2

Participants received MK-8776 10 mg/m^2 given as monotherapy as an intravenous (IV) infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle.

Drug: MK-8776
IV infusion
Other Names:
  • SCH 900776

    • Drug: Gemcitabine
    IV infusion
    Other Names:
  • GEMZAR®

    		•
    Experimental: MK-8776 20mg/m^2+Gemcitabine 800mg/m^2

    Participants received MK-8776 20 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle.

    Drug: MK-8776
    IV infusion
    Other Names:
  • SCH 900776

    • Drug: Gemcitabine
    IV infusion
    Other Names:
  • GEMZAR®

    		•
    Experimental: MK-8776 40mg/m^2+Gemcitabine 800mg/m^2

    Participants received MK-8776 40 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle.

    Drug: MK-8776
    IV infusion
    Other Names:
  • SCH 900776

    • Drug: Gemcitabine
    IV infusion
    Other Names:
  • GEMZAR®

    		•
    Experimental: MK-8776 80mg/m^2+Gemcitabine 800mg/m^2

    Participants received MK-8776 80 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle.

    Drug: MK-8776
    IV infusion
    Other Names:
  • SCH 900776

    • Drug: Gemcitabine
    IV infusion
    Other Names:
  • GEMZAR®

    		•
    Experimental: MK-8776 112mg/m^2+Gemcitabine 800mg/m^2

    Participants received MK-8776 112 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle.

    Drug: MK-8776
    IV infusion
    Other Names:
  • SCH 900776

    • Drug: Gemcitabine
    IV infusion
    Other Names:
  • GEMZAR®

    		•
    Experimental: MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2

    Participants received MK-8776 80 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle.

    Drug: MK-8776
    IV infusion
    Other Names:
  • SCH 900776

    • Drug: Gemcitabine
    IV infusion
    Other Names:
  • GEMZAR®

    		•
    Experimental: MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2

    Participants received MK-8776 112 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle.

    Drug: MK-8776
    IV infusion
    Other Names:
  • SCH 900776

    • Drug: Gemcitabine
    IV infusion
    Other Names:
  • GEMZAR®

    		•
    Experimental: MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2

    Participants received MK-8776 150 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle.

    Drug: MK-8776
    IV infusion
    Other Names:
  • SCH 900776

    • Drug: Gemcitabine
    IV infusion
    Other Names:
  • GEMZAR®

    		•
    Experimental: MK-8776 200mg+Gemcitabine 1000mg/m^2

    Participants received MK-8776 200 mg given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle.

    Drug: MK-8776
    IV infusion
    Other Names:
  • SCH 900776

    • Drug: Gemcitabine
    IV infusion
    Other Names:
  • GEMZAR®

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) During Cycle 0 and Cycle 1 Based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE v 3.0) [Through Cycle 0 and Cycle 1 (Up to 42 days)]

      During Cycle 0, a DLT was defined as: CTCAE v 3.0 Grade 3 neutropenia or thrombocytopenia lasting ≥3 days; any CTCAE v 3.0 Grade 4 neutropenia or thrombocytopenia; neutropenic fever; any CTCAE v. 3.0 ≥ Grade 3 QT interval corrected by Fridericia (QTcF) prolongation of any duration; any other CTCAE v 3.0 Grade 3 or higher nonhematologic toxicity; or Grade 3 elevation of transaminases that resolved prior to administration of next dose(s) of study drug(s); delay in Cycle 1 Day 1 beyond 3 weeks due to continuing toxicity. During Cycle 1, a DLT was defined as: CTCAE v 3.0 Grade 4 neutropenia that persists for ≥7 days; neutropenic fever; CTCAE v 3.0 Grade 4 thrombocytopenia; CTCAE v 3.0 ≥ Grade 3 thrombocytopenia with bleeding; any CTCAE v 3.0 QTc ≥ Grade 3 QTcF prolongation of any duration; any other CTCAE v 3.0 Grade 3 or higher nonhematologic toxicity; or Grade 3 elevation of transaminases that resolved prior to administration of next dose(s) of study drug(s).

    2. Number of Participants Who Experienced an Adverse Event (AE) [Up to approximately 72 weeks (Up to approximately 6 weeks after last dose of study treatment)]

      An AE was defined as any untoward medical occurrence in a participant administered study treatment which did not necessarily have to have a causal relationship with this treatment. An AE could have been any unfavorable and unintended sign (e.g. an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to study treatment. The number of participants who experienced an AE is presented.

    3. Number of Participants Who Discontinued Study Treatment Due to an AE [Up to approximatey 66 weeks]

      An AE was defined as any untoward medical occurrence in a participant administered study treatment which did not necessarily have to have a causal relationship with this treatment. An AE could have been any unfavorable and unintended sign (e.g. an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to study treatment. The number of participants who discontinued study treatment due to an AE is presented.

    Secondary Outcome Measures

    1. MK-8776 Maximum Plasma Concentration (Cmax) [At end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion]

      The Cmax of MK-8776 was assessed in Cycle 0 and in Cycle 1. On Day 1 of Cycle 0 and Cycle 1, plasma samples were obtained from all participants before infusion, at end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion.

    2. MK-8776 Area Under the Curve of the Plasma Concentration Versus Time From Time Zero to the Time of the Last Analytically Quantifiable Concentration (AUC0-last) [At end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion]

      AUC0-last was assessed in Cycle 0 and in Cycle 1. On Day 1 of Cycle 0 and Cycle 1, plasma samples were obtained from all participants before infusion, at end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion. AUC0-last was calculated by the linear trapezoidal method.

    3. Time of MK-8776 Cmax (Tmax) [At end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion]

      The time of Cmax of MK-8776 was assessed in Cycle 0 and in Cycle 1. On Day 1 of Cycle 0 and Cycle 1, plasma samples were obtained from all participants before infusion, at end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion.

    4. MK-8776 Terminal Phase Half-Life (t1/2) [At end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion]

      The t1/2 of MK-8776 was assessed in Cycle 0 and in Cycle 1. On Day 1 of Cycle 0 and Cycle 1, plasma samples were obtained from all participants before infusion, at end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Must have a diagnosis of an advanced solid tumor malignancy or lymphoma (non-Hodgkin's or Hodgkin's lymphoma).

    • Must have histological or cytological evidence of malignancy.

    • Must have an advanced malignancy, metastatic or unresectable. For Part A of the study, the metastatic or unresectable malignancy should have recurred or progressed following standard therapy or failed standard therapy; or for which no standard therapy currently exists, or for which they are not candidates for standard therapy. For Parts B and C of the study, participants with advanced tumors for which gemcitabine is considered standard therapy (eg, pancreatic cancer), may be enrolled without having received prior gemcitabine. Standard therapy is defined as therapy that is approved in a particular line of therapy or considered as standard of care based on published peer reviewed data in a specific line of therapy.

    • Gemcitabine-naïve participants with tumors known to be responsive to gemcitabine or participants previously treated with gemcitabine who did not progress while on treatment or who are currently still responding to treatment should only be enrolled in cohorts for which gemcitabine doses are >=1000 mg/m². Participants previously treated with gemcitabine, whose disease has progressed wile on treatment, can be enrolled to any part.

    • Must be ambulatory with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

    • Participants (and/or parent/guardian for participants who otherwise are unable to provide independent consent) must be willing to give written informed consent and able to adhere to dose and visit schedules.

    • Female participants of childbearing potential must have a negative pregnancy test within 7 days of first dose of protocol therapy.

    • Female participants of childbearing potential and male participants whose sexual partners are of childbearing potential must agree to abstain from sexual intercourse or to use an acceptable method of contraception during the study and for 90 days following the last dose of protocol therapy. Acceptable methods of contraception include condoms (male or female) with or without spermicidal agent, diaphragm or cervical cap with spermicide, medically prescribed intrauterine device (IUD), oral or injectable hormonal contraceptive, and surgical sterilization (eg, hysterectomy or tubal ligation).

    • Must have adequate bone marrow reserve as evidenced by a white blood cell (WBC) count

    =3,000/ μL, absolute neutrophil count (ANC) >=1,500/μL AND platelet count =100,000/μL.

    • Must have adequate renal function as evidenced by a serum creatinine level <=1.5 x upper limit of normal (ULN) or a calculated creatinine clearance >60 mL/min.

    • Participants, except those with known Gilbert's Syndrome, must have adequate hepatic function as evidenced by a serum bilirubin level <=1.5 x the ULN AND serum levels of aspartate and alanine aminotransferase (AST/ALT) levels <=3 x the ULN for the reference lab (participants with known hepatic metastases must have serum AST/ALT levels <=5 x the ULN for the reference lab).

    • Must be recovered from the effects of any prior surgery, radiotherapy or systemic antineoplastic therapy.

    Exclusion Criteria:

    • Has a known hypersensitivity to MK-8776 or gemcitabine or to any of their excipients or has received therapy with another Checkpoint kinase 1 (CHK1) inhibitor.

    • Has received any prohibited medication more recently than the indicated washout period prior to first dose of protocol therapy or must continue to receive prohibited medications. Prohibited medications: cytochrome P450 1A2 inhibitors, any chemotherapy, or investigational drugs.

    • Has significant underlying cardiac conduction system abnormalities such as bifascicular or greater block (eg, right bundle branch block with left anterior hemiblock or first degree atrioventricular block), fixed-rate pacemaker, or chronic atrial fibrillation with variable ventricular rate.

    • Has persistent, unresolved Common Terminology Criteria for Adverse Events (CTCAE) v 3.0 >=Grade 2 drug-related toxicity (except alopecia, erectile impotence, hot flashes, and decreased libido) associated with previous treatment.

    • Has known human immunodeficiency virus (HIV), hepatitis B, hepatitis C, or a known history of liver cirrhosis or active alcohol abuse.

    • Is New York Heart Association (NYHA) Class III.

    • Has any other medical or psychiatric condition that, in the opinion of the investigator, might interfere with the subject's participation in the trial or interfere with the interpretation of trial results.

    • Has undergone major surgery within 3 weeks prior to first study drug administration after enrollment.

    • Has central nervous system (CNS) or leptomeningeal metastases.

    • Has received radiation therapy within 3 weeks prior to first study drug administration after enrollment or radiation therapy to >25% of bone marrow.

    • Has received >3 prior chemotherapy regimens (may have received prior gemcitabine). A participant may not have experienced any CTCAE v 3.0 >Grade 1 myelotoxicity (neutropenia and/or thrombocytopenia) with any prior regimen, including gemcitabine. Participants with >3 prior chemotherapy regimens, one or more of which were targeted, nonmyelosuppressive agents, may be considered on a case-by-case basis after discussion with the sponsor.

    • Has undergone previous allogeneic or autologous stem cell transplant.

    • Has had any of the following within 6 months prior to first study drug administration after enrollment: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or seizure disorder.

    • Has a known bleeding diathesis, eg, hemophilia.

    • Has a baseline QTc interval >450 msec (ie, CTCAE v 3.0 Grade ≥2) at screening (within 21 days prior to 1st dose of MK-8776, mean of triplicate readings within approximately 5 minutes).

    • History of risk factors for Torsades de Pointes, including clinical history of heart failure, hypo- or hyperkalemia or hypomagnesemia (supplementation or other appropriate interventions to bring levels within normal institutional limits prior to administration of MK-8776 is acceptable), or family history of Long QT Syndrome.

    • Currently a smoker and/or is likely to smoke during the study.

    • Female participant who is breast-feeding, pregnant, or intends to become pregnant.

    • Participating in any other interventional clinical study. (Participants participating in another noninterventional study may be considered after discussion with the sponsor.)

    • Part of the staff personnel directly related to this study.

    • Family member of one of the investigational staff.

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Merck Sharp & Dohme LLC

    Investigators

    • Study Director: Medical Director, Merck Sharp & Dohme LLC

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Merck Sharp & Dohme LLC
    ClinicalTrials.gov Identifier:
    NCT00779584
    Other Study ID Numbers:
    • P05248
    • MK-8776-002
    First Posted:
    Oct 24, 2008
    Last Update Posted:
    Aug 27, 2018
    Last Verified:
    Jul 1, 2018
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Additional relevant MeSH terms:
    Lymphoma
    Hodgkin Disease
    Lymphoma, Non-Hodgkin
    Gemcitabine

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title MK-8776 10mg/m^2+Gemcitabine 800mg/m^2 MK-8776 20mg/m^2+Gemcitabine 800mg/m^2 MK-8776 40mg/m^2+Gemcitabine 800mg/m^2 MK-8776 80mg/m^2+Gemcitabine 800mg/m^2 MK-8776 112mg/m^2+Gemcitabine 800mg/m^2 MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2 MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2 MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2 MK-8776 200mg+Gemcitabine 1000mg/m^2
    Arm/Group Description Participants received MK-8776 10 mg/m^2 given as monotherapy as an intravenous (IV) infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 20 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 40 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 80 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 112 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 80 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 112 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 150 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 200 mg given as a flat dose monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle.
    Period Title: Overall Study
    STARTED 3 3 7 6 7 6 8 3 2
    Treated 3 3 7 6 7 4 8 3 2
    COMPLETED 0 0 0 0 0 0 0 0 0
    NOT COMPLETED 3 3 7 6 7 6 8 3 2

    Baseline Characteristics

    Arm/Group Title MK-8776 10mg/m^2+Gemcitabine 800mg/m^2 MK-8776 20mg/m^2+Gemcitabine 800mg/m^2 MK-8776 40mg/m^2+Gemcitabine 800mg/m^2 MK-8776 80mg/m^2+Gemcitabine 800mg/m^2 MK-8776 112mg/m^2+Gemcitabine 800mg/m^2 MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2 MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2 MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2 MK-8776 200mg+Gemcitabine 1000mg/m^2 Total
    Arm/Group Description Participants received MK-8776 10 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 20 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 40 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 80 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 112 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 80 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 112 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 150 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 200 mg given as a flat dose monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Total of all reporting groups
    Overall Participants 3 3 7 6 7 6 8 3 2 45
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    54.3
    (16.0)
    54.3
    (8.6)
    64.0
    (16.1)
    55.5
    (5.0)
    51.1
    (5.7)
    59.0
    (13.4)
    59.9
    (9.1)
    69.3
    (5.5)
    69.0
    (8.5)
    58.8
    (11.2)
    Sex: Female, Male (Count of Participants)
    Female
    2
    66.7%
    0
    0%
    2
    28.6%
    2
    33.3%
    4
    57.1%
    2
    33.3%
    3
    37.5%
    1
    33.3%
    2
    100%
    18
    40%
    Male
    1
    33.3%
    3
    100%
    5
    71.4%
    4
    66.7%
    3
    42.9%
    4
    66.7%
    5
    62.5%
    2
    66.7%
    0
    0%
    27
    60%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) During Cycle 0 and Cycle 1 Based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE v 3.0)
    Description During Cycle 0, a DLT was defined as: CTCAE v 3.0 Grade 3 neutropenia or thrombocytopenia lasting ≥3 days; any CTCAE v 3.0 Grade 4 neutropenia or thrombocytopenia; neutropenic fever; any CTCAE v. 3.0 ≥ Grade 3 QT interval corrected by Fridericia (QTcF) prolongation of any duration; any other CTCAE v 3.0 Grade 3 or higher nonhematologic toxicity; or Grade 3 elevation of transaminases that resolved prior to administration of next dose(s) of study drug(s); delay in Cycle 1 Day 1 beyond 3 weeks due to continuing toxicity. During Cycle 1, a DLT was defined as: CTCAE v 3.0 Grade 4 neutropenia that persists for ≥7 days; neutropenic fever; CTCAE v 3.0 Grade 4 thrombocytopenia; CTCAE v 3.0 ≥ Grade 3 thrombocytopenia with bleeding; any CTCAE v 3.0 QTc ≥ Grade 3 QTcF prolongation of any duration; any other CTCAE v 3.0 Grade 3 or higher nonhematologic toxicity; or Grade 3 elevation of transaminases that resolved prior to administration of next dose(s) of study drug(s).
    Time Frame Through Cycle 0 and Cycle 1 (Up to 42 days)

    Outcome Measure Data

    Analysis Population Description
    The population consisted of all participants who were evaluable for DLT assessment (i.e., completed Cycle 0 and Cycle 1).
    Arm/Group Title MK-8776 10mg/m^2+Gemcitabine 800mg/m^2 MK-8776 20mg/m^2+Gemcitabine 800mg/m^2 MK-8776 40mg/m^2+Gemcitabine 800mg/m^2 MK-8776 80mg/m^2+Gemcitabine 800mg/m^2 MK-8776 112mg/m^2+Gemcitabine 800mg/m^2 MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2 MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2 MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2 MK-8776 200mg+Gemcitabine 1000mg/m^2
    Arm/Group Description Participants received MK-8776 10 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 20 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 40 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 80 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 112 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 80 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 112 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 150 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 200 mg given as a flat dose monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle.
    Measure Participants 3 3 7 6 7 4 6 3 2
    Number [Participants]
    0
    0%
    0
    0%
    1
    14.3%
    0
    0%
    2
    28.6%
    0
    0%
    1
    12.5%
    0
    0%
    0
    0%
    2. Primary Outcome
    Title Number of Participants Who Experienced an Adverse Event (AE)
    Description An AE was defined as any untoward medical occurrence in a participant administered study treatment which did not necessarily have to have a causal relationship with this treatment. An AE could have been any unfavorable and unintended sign (e.g. an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to study treatment. The number of participants who experienced an AE is presented.
    Time Frame Up to approximately 72 weeks (Up to approximately 6 weeks after last dose of study treatment)

    Outcome Measure Data

    Analysis Population Description
    The population consisted of all participants who received at least one dose of MK-8776.
    Arm/Group Title MK-8776 10mg/m^2+Gemcitabine 800mg/m^2 MK-8776 20mg/m^2+Gemcitabine 800mg/m^2 MK-8776 40mg/m^2+Gemcitabine 800mg/m^2 MK-8776 80mg/m^2+Gemcitabine 800mg/m^2 MK-8776 112mg/m^2+Gemcitabine 800mg/m^2 MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2 MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2 MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2 MK-8776 200mg+Gemcitabine 1000mg/m^2
    Arm/Group Description Participants received MK-8776 10 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 20 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 40 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 80 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 112 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 80 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 112 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 150 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 200 mg given as a flat dose monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle.
    Measure Participants 3 3 7 6 7 4 8 3 2
    Number [Participants]
    3
    100%
    3
    100%
    7
    100%
    6
    100%
    7
    100%
    4
    66.7%
    8
    100%
    3
    100%
    2
    100%
    3. Primary Outcome
    Title Number of Participants Who Discontinued Study Treatment Due to an AE
    Description An AE was defined as any untoward medical occurrence in a participant administered study treatment which did not necessarily have to have a causal relationship with this treatment. An AE could have been any unfavorable and unintended sign (e.g. an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to study treatment. The number of participants who discontinued study treatment due to an AE is presented.
    Time Frame Up to approximatey 66 weeks

    Outcome Measure Data

    Analysis Population Description
    The population consisted of all participants who received at least one dose of MK-8776.
    Arm/Group Title MK-8776 10mg/m^2+Gemcitabine 800mg/m^2 MK-8776 20mg/m^2+Gemcitabine 800mg/m^2 MK-8776 40mg/m^2+Gemcitabine 800mg/m^2 MK-8776 80mg/m^2+Gemcitabine 800mg/m^2 MK-8776 112mg/m^2+Gemcitabine 800mg/m^2 MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2 MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2 MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2 MK-8776 200mg+Gemcitabine 1000mg/m^2
    Arm/Group Description Participants received MK-8776 10 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 20 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 40 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 80 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 112 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 80 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 112 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 150 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 200 mg given as a flat dose monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle.
    Measure Participants 3 3 7 6 7 4 8 3 2
    Number [Participants]
    1
    33.3%
    0
    0%
    2
    28.6%
    0
    0%
    0
    0%
    0
    0%
    2
    25%
    1
    33.3%
    1
    50%
    4. Secondary Outcome
    Title MK-8776 Maximum Plasma Concentration (Cmax)
    Description The Cmax of MK-8776 was assessed in Cycle 0 and in Cycle 1. On Day 1 of Cycle 0 and Cycle 1, plasma samples were obtained from all participants before infusion, at end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion.
    Time Frame At end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion

    Outcome Measure Data

    Analysis Population Description
    The population consisted of all participants who received at least two cycles of study treatment.
    Arm/Group Title MK-8776 10mg/m^2+Gemcitabine 800mg/m^2 MK-8776 20mg/m^2+Gemcitabine 800mg/m^2 MK-8776 40mg/m^2+Gemcitabine 800mg/m^2 MK-8776 80mg/m^2+Gemcitabine 800mg/m^2 MK-8776 112mg/m^2+Gemcitabine 800mg/m^2 MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2 MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2 MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2 MK-8776 200mg+Gemcitabine 1000mg/m^2
    Arm/Group Description Participants received MK-8776 10 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 20 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 40 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 80 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 112 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 80 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 112 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 150 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 200 mg given as a flat dose monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle.
    Measure Participants 3 3 7 6 7 4 8 3 2
    Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2)
    414
    (257)
    1010
    (197)
    1220
    (366)
    4970
    (1500)
    5270
    (3730)
    2960
    (1290)
    6210
    (2160)
    6220
    (2550)
    4860
    (NA)
    Cycle 1 (n=3, 3, 7, 5, 6, 4, 6, 1, 2)
    445
    (249)
    1650
    (1520)
    962
    (454)
    3700
    (1930)
    4710
    (2310)
    3610
    (2290)
    4690
    (2610)
    4940
    (NA)
    3700
    (NA)
    5. Secondary Outcome
    Title MK-8776 Area Under the Curve of the Plasma Concentration Versus Time From Time Zero to the Time of the Last Analytically Quantifiable Concentration (AUC0-last)
    Description AUC0-last was assessed in Cycle 0 and in Cycle 1. On Day 1 of Cycle 0 and Cycle 1, plasma samples were obtained from all participants before infusion, at end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion. AUC0-last was calculated by the linear trapezoidal method.
    Time Frame At end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion

    Outcome Measure Data

    Analysis Population Description
    The population consisted of all participants who received at least two cycles of study treatment.
    Arm/Group Title MK-8776 10mg/m^2+Gemcitabine 800mg/m^2 MK-8776 20mg/m^2+Gemcitabine 800mg/m^2 MK-8776 40mg/m^2+Gemcitabine 800mg/m^2 MK-8776 80mg/m^2+Gemcitabine 800mg/m^2 MK-8776 112mg/m^2+Gemcitabine 800mg/m^2 MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2 MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2 MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2 MK-8776 200mg+Gemcitabine 1000mg/m^2
    Arm/Group Description Participants received MK-8776 10 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 20 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 40 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 80 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 112 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 80 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 112 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 150 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 200 mg given as a flat dose monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle.
    Measure Participants 3 3 7 6 7 4 8 3 2
    Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2)
    565
    (171)
    1400
    (448)
    2250
    (948)
    5060
    (1920)
    9050
    (5500)
    4040
    (1010)
    9240
    (5740)
    18500
    (8000)
    8440
    (NA)
    Cycle 1 (n=3, 3, 7, 5, 6, 4, 6, 1, 2)
    539
    (307)
    1570
    (423)
    1900
    (859)
    4540
    (1660)
    10300
    (6370)
    4660
    (815)
    6900
    (3120)
    13000
    (NA)
    16900
    (NA)
    6. Secondary Outcome
    Title Time of MK-8776 Cmax (Tmax)
    Description The time of Cmax of MK-8776 was assessed in Cycle 0 and in Cycle 1. On Day 1 of Cycle 0 and Cycle 1, plasma samples were obtained from all participants before infusion, at end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion.
    Time Frame At end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion

    Outcome Measure Data

    Analysis Population Description
    The population consisted of all participants who received at least two cycles of study treatment.
    Arm/Group Title MK-8776 10mg/m^2+Gemcitabine 800mg/m^2 MK-8776 20mg/m^2+Gemcitabine 800mg/m^2 MK-8776 40mg/m^2+Gemcitabine 800mg/m^2 MK-8776 80mg/m^2+Gemcitabine 800mg/m^2 MK-8776 112mg/m^2+Gemcitabine 800mg/m^2 MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2 MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2 MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2 MK-8776 200mg+Gemcitabine 1000mg/m^2
    Arm/Group Description Participants received MK-8776 10 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 20 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 40 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 80 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 112 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 80 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 112 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 150 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 200 mg given as a flat dose monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle.
    Measure Participants 3 3 7 6 7 4 8 3 2
    Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2)
    0.27
    (0.03)
    0.26
    (0.01)
    0.29
    (0.06)
    0.24
    (0.03)
    0.30
    (0.08)
    0.26
    (0.05)
    0.23
    (0.02)
    0.48
    (0.02)
    0.49
    (NA)
    Cycle 1 (n=3, 3, 7, 5, 6, 4, 6, 1, 2)
    0.26
    (0.01)
    0.27
    (0.02)
    0.35
    (0.13)
    0.25
    (0.06)
    0.28
    (0.06)
    0.26
    (0.03)
    0.23
    (0.01)
    0.50
    (NA)
    0.57
    (NA)
    7. Secondary Outcome
    Title MK-8776 Terminal Phase Half-Life (t1/2)
    Description The t1/2 of MK-8776 was assessed in Cycle 0 and in Cycle 1. On Day 1 of Cycle 0 and Cycle 1, plasma samples were obtained from all participants before infusion, at end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion.
    Time Frame At end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion

    Outcome Measure Data

    Analysis Population Description
    The population consisted of all participants who received at least two cycles of study treatment.
    Arm/Group Title MK-8776 10mg/m^2+Gemcitabine 800mg/m^2 MK-8776 20mg/m^2+Gemcitabine 800mg/m^2 MK-8776 40mg/m^2+Gemcitabine 800mg/m^2 MK-8776 80mg/m^2+Gemcitabine 800mg/m^2 MK-8776 112mg/m^2+Gemcitabine 800mg/m^2 MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2 MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2 MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2 MK-8776 200mg+Gemcitabine 1000mg/m^2
    Arm/Group Description Participants received MK-8776 10 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 20 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 40 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 80 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 112 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 80 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 112 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 150 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 200 mg given as a flat dose monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle.
    Measure Participants 3 3 7 6 7 4 8 3 3
    Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2)
    6.29
    (1.97)
    9.33
    (5.09)
    8.45
    (2.95)
    7.44
    (0.435)
    5.94
    (1.62)
    8.13
    (1.30)
    7.14
    (1.90)
    9.46
    (2.11)
    6.30
    (NA)
    Cycle 1 (n=3, 3, 6, 6, 7, 4, 7, 1, 2)
    6.24
    (2.03)
    8.57
    (4.54)
    8.23
    (1.71)
    9.01
    (2.51)
    7.29
    (1.26)
    7.87
    (2.11)
    7.98
    (1.21)
    7.59
    (NA)
    9.89
    (NA)

    Adverse Events

    Time Frame Up to approximately 72 weeks (Up to approximately 6 weeks after last dose of study treatment)
    Adverse Event Reporting Description The population consisted of all participants who received at least one dose of MK-8776.
    Arm/Group Title MK-8776 10mg/m^2+Gemcitabine 800mg/m^2 MK-8776 20mg/m^2+Gemcitabine 800mg/m^2 MK-8776 40mg/m^2+Gemcitabine 800mg/m^2 MK-8776 80mg/m^2+Gemcitabine 800mg/m^2 MK-8776 112mg/m^2+Gemcitabine 800mg/m^2 MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2 MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2 MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2 MK-8776 200mg Flat Dose+Gemcitabine 1000mg/m^2
    Arm/Group Description Participants received MK-8776 10 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 20 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 40 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 80 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 112 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 80 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 112 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 150 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Participants received MK-8776 200 mg given as a flat dose monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle.
    All Cause Mortality
    MK-8776 10mg/m^2+Gemcitabine 800mg/m^2 MK-8776 20mg/m^2+Gemcitabine 800mg/m^2 MK-8776 40mg/m^2+Gemcitabine 800mg/m^2 MK-8776 80mg/m^2+Gemcitabine 800mg/m^2 MK-8776 112mg/m^2+Gemcitabine 800mg/m^2 MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2 MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2 MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2 MK-8776 200mg Flat Dose+Gemcitabine 1000mg/m^2
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events 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) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    MK-8776 10mg/m^2+Gemcitabine 800mg/m^2 MK-8776 20mg/m^2+Gemcitabine 800mg/m^2 MK-8776 40mg/m^2+Gemcitabine 800mg/m^2 MK-8776 80mg/m^2+Gemcitabine 800mg/m^2 MK-8776 112mg/m^2+Gemcitabine 800mg/m^2 MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2 MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2 MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2 MK-8776 200mg Flat Dose+Gemcitabine 1000mg/m^2
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/3 (66.7%) 1/3 (33.3%) 3/7 (42.9%) 1/6 (16.7%) 2/7 (28.6%) 3/4 (75%) 4/8 (50%) 0/3 (0%) 2/2 (100%)
    Cardiac disorders
    ATRIAL FIBRILLATION 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    CARDIOMYOPATHY 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    SUPRAVENTRICULAR TACHYCARDIA 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    Gastrointestinal disorders
    ABDOMINAL PAIN 1/3 (33.3%) 1 1/3 (33.3%) 1 1/7 (14.3%) 1 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 1/2 (50%) 2
    CONSTIPATION 1/3 (33.3%) 1 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    DUODENAL OBSTRUCTION 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/4 (25%) 1 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    ENTEROCUTANEOUS FISTULA 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    VOMITING 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/4 (25%) 1 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    General disorders
    CHEST PAIN 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 0/2 (0%) 0
    PYREXIA 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 1/4 (25%) 1 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    Hepatobiliary disorders
    CHOLANGITIS 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 1/2 (50%) 1
    HYPERBILIRUBINAEMIA 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/4 (25%) 1 1/8 (12.5%) 1 0/3 (0%) 0 0/2 (0%) 0
    Infections and infestations
    ABDOMINAL ABSCESS 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    MASTOIDITIS 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    PNEUMOCYSTIS JIROVECI PNEUMONIA 1/3 (33.3%) 1 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    PNEUMONIA 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    Injury, poisoning and procedural complications
    HIP FRACTURE 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 1/2 (50%) 1
    Investigations
    ELECTROCARDIOGRAM QT PROLONGED 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 0/2 (0%) 0
    Metabolism and nutrition disorders
    DEHYDRATION 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    MALIGNANT MELANOMA 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/4 (25%) 1 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    Nervous system disorders
    CONVULSION 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    NEUROLOGICAL SYMPTOM 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/4 (25%) 1 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    SYNCOPE 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/4 (25%) 1 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    Psychiatric disorders
    ANXIETY 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 0/2 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    DYSPNOEA 1/3 (33.3%) 1 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    Other (Not Including Serious) Adverse Events
    MK-8776 10mg/m^2+Gemcitabine 800mg/m^2 MK-8776 20mg/m^2+Gemcitabine 800mg/m^2 MK-8776 40mg/m^2+Gemcitabine 800mg/m^2 MK-8776 80mg/m^2+Gemcitabine 800mg/m^2 MK-8776 112mg/m^2+Gemcitabine 800mg/m^2 MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2 MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2 MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2 MK-8776 200mg Flat Dose+Gemcitabine 1000mg/m^2
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/3 (100%) 3/3 (100%) 7/7 (100%) 6/6 (100%) 7/7 (100%) 4/4 (100%) 8/8 (100%) 3/3 (100%) 2/2 (100%)
    Blood and lymphatic system disorders
    ANAEMIA 0/3 (0%) 0 1/3 (33.3%) 1 1/7 (14.3%) 1 1/6 (16.7%) 1 2/7 (28.6%) 4 1/4 (25%) 1 2/8 (25%) 3 1/3 (33.3%) 1 0/2 (0%) 0
    LEUKOPENIA 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    LYMPHOPENIA 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 0/2 (0%) 0
    NEUTROPENIA 0/3 (0%) 0 0/3 (0%) 0 2/7 (28.6%) 4 1/6 (16.7%) 1 1/7 (14.3%) 1 2/4 (50%) 7 4/8 (50%) 13 0/3 (0%) 0 0/2 (0%) 0
    THROMBOCYTOPENIA 1/3 (33.3%) 1 0/3 (0%) 0 1/7 (14.3%) 2 2/6 (33.3%) 4 3/7 (42.9%) 6 1/4 (25%) 1 4/8 (50%) 6 1/3 (33.3%) 2 0/2 (0%) 0
    Cardiac disorders
    SINUS TACHYCARDIA 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 1/2 (50%) 1
    Ear and labyrinth disorders
    EUSTACHIAN TUBE OBSTRUCTION 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    MIDDLE EAR EFFUSION 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 0/2 (0%) 0
    Eye disorders
    EYE IRRITATION 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    EYE PAIN 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    VISUAL IMPAIRMENT 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    Gastrointestinal disorders
    ABDOMINAL DISTENSION 1/3 (33.3%) 1 0/3 (0%) 0 1/7 (14.3%) 2 0/6 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 2/8 (25%) 2 0/3 (0%) 0 0/2 (0%) 0
    ABDOMINAL PAIN 2/3 (66.7%) 4 0/3 (0%) 0 1/7 (14.3%) 5 2/6 (33.3%) 2 1/7 (14.3%) 1 2/4 (50%) 2 2/8 (25%) 2 0/3 (0%) 0 0/2 (0%) 0
    ABDOMINAL PAIN UPPER 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/4 (25%) 1 2/8 (25%) 2 0/3 (0%) 0 0/2 (0%) 0
    ASCITES 1/3 (33.3%) 1 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 3 0/7 (0%) 0 1/4 (25%) 2 0/8 (0%) 0 0/3 (0%) 0 1/2 (50%) 2
    COLITIS 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    CONSTIPATION 1/3 (33.3%) 1 1/3 (33.3%) 2 1/7 (14.3%) 1 3/6 (50%) 4 2/7 (28.6%) 2 1/4 (25%) 1 3/8 (37.5%) 3 0/3 (0%) 0 1/2 (50%) 1
    DENTAL DISCOMFORT 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 0/2 (0%) 0
    DIARRHOEA 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 1/6 (16.7%) 1 1/7 (14.3%) 2 1/4 (25%) 2 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    DRY MOUTH 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 0/2 (0%) 0
    DYSPEPSIA 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    FAECAL INCONTINENCE 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/4 (25%) 1 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    GASTRITIS 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    GASTROOESOPHAGEAL REFLUX DISEASE 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 1/4 (25%) 1 0/8 (0%) 0 1/3 (33.3%) 1 1/2 (50%) 1
    GINGIVAL PAIN 1/3 (33.3%) 1 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    HAEMATOCHEZIA 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 0/2 (0%) 0
    HAEMORRHOIDAL HAEMORRHAGE 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    NAUSEA 3/3 (100%) 5 1/3 (33.3%) 1 2/7 (28.6%) 5 3/6 (50%) 3 4/7 (57.1%) 6 3/4 (75%) 5 2/8 (25%) 3 3/3 (100%) 3 1/2 (50%) 1
    RECTAL HAEMORRHAGE 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/4 (25%) 1 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    SALIVARY GLAND ENLARGEMENT 1/3 (33.3%) 1 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    SENSITIVITY OF TEETH 1/3 (33.3%) 1 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    STOMATITIS 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    VOMITING 2/3 (66.7%) 2 0/3 (0%) 0 2/7 (28.6%) 2 1/6 (16.7%) 3 4/7 (57.1%) 4 1/4 (25%) 1 0/8 (0%) 0 1/3 (33.3%) 1 0/2 (0%) 0
    General disorders
    ASTHENIA 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/7 (0%) 0 1/4 (25%) 1 1/8 (12.5%) 1 0/3 (0%) 0 0/2 (0%) 0
    CATHETER SITE HAEMATOMA 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 0/2 (0%) 0
    CATHETER SITE PAIN 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    CHEST DISCOMFORT 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    CHEST PAIN 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 0/2 (0%) 0
    CHILLS 0/3 (0%) 0 1/3 (33.3%) 2 2/7 (28.6%) 2 0/6 (0%) 0 1/7 (14.3%) 1 1/4 (25%) 1 2/8 (25%) 2 0/3 (0%) 0 0/2 (0%) 0
    EARLY SATIETY 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    FATIGUE 2/3 (66.7%) 2 2/3 (66.7%) 4 5/7 (71.4%) 6 5/6 (83.3%) 7 6/7 (85.7%) 9 4/4 (100%) 10 4/8 (50%) 6 1/3 (33.3%) 1 0/2 (0%) 0
    GENERALISED OEDEMA 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 1/2 (50%) 1
    INFLUENZA LIKE ILLNESS 1/3 (33.3%) 3 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    INFUSION SITE PAIN 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    MUCOSAL INFLAMMATION 1/3 (33.3%) 1 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    NON-CARDIAC CHEST PAIN 0/3 (0%) 0 2/3 (66.7%) 3 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    OEDEMA 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 1/2 (50%) 1
    OEDEMA PERIPHERAL 1/3 (33.3%) 1 0/3 (0%) 0 4/7 (57.1%) 5 3/6 (50%) 3 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 1/2 (50%) 1
    PAIN 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 1/6 (16.7%) 1 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    PYREXIA 1/3 (33.3%) 2 1/3 (33.3%) 2 2/7 (28.6%) 2 2/6 (33.3%) 3 2/7 (28.6%) 2 1/4 (25%) 1 1/8 (12.5%) 1 0/3 (0%) 0 1/2 (50%) 1
    Hepatobiliary disorders
    BILE DUCT OBSTRUCTION 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 1/3 (33.3%) 1 0/2 (0%) 0
    BILIARY DILATATION 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/4 (25%) 1 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    HEPATIC PAIN 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/4 (25%) 1 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    HYPERBILIRUBINAEMIA 1/3 (33.3%) 1 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/7 (0%) 0 1/4 (25%) 3 0/8 (0%) 0 1/3 (33.3%) 2 1/2 (50%) 1
    Infections and infestations
    CANDIDIASIS 1/3 (33.3%) 2 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    CATHETER SITE INFECTION 0/3 (0%) 0 1/3 (33.3%) 1 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    CELLULITIS 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 1/2 (50%) 1
    EYE INFECTION 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    HERPES ZOSTER 1/3 (33.3%) 1 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    NASOPHARYNGITIS 0/3 (0%) 0 1/3 (33.3%) 1 0/7 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 1/4 (25%) 1 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    ORAL CANDIDIASIS 1/3 (33.3%) 2 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    ORAL HERPES 1/3 (33.3%) 2 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    RESPIRATORY TRACT INFECTION 0/3 (0%) 0 1/3 (33.3%) 1 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    SINUSITIS 0/3 (0%) 0 1/3 (33.3%) 1 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    TINEA MANUUM 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 2 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    UPPER RESPIRATORY TRACT INFECTION 1/3 (33.3%) 2 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 1/4 (25%) 1 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    URINARY TRACT INFECTION 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 1/2 (50%) 1
    Injury, poisoning and procedural complications
    CONTUSION 0/3 (0%) 0 1/3 (33.3%) 1 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    EXCORIATION 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 2/6 (33.3%) 2 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    MUSCLE STRAIN 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    PROCEDURAL PAIN 1/3 (33.3%) 1 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    TRANSFUSION REACTION 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/4 (25%) 1 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    Investigations
    ALANINE AMINOTRANSFERASE INCREASED 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    ASPARTATE AMINOTRANSFERASE INCREASED 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    BLOOD ALKALINE PHOSPHATASE INCREASED 1/3 (33.3%) 1 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/8 (12.5%) 2 0/3 (0%) 0 0/2 (0%) 0
    BLOOD CREATININE INCREASED 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/4 (25%) 1 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    BLOOD PRESSURE INCREASED 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 0/2 (0%) 0
    BREATH SOUNDS ABNORMAL 0/3 (0%) 0 1/3 (33.3%) 1 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    ELECTROCARDIOGRAM QT PROLONGED 0/3 (0%) 0 0/3 (0%) 0 2/7 (28.6%) 3 0/6 (0%) 0 1/7 (14.3%) 25 1/4 (25%) 5 2/8 (25%) 7 3/3 (100%) 5 1/2 (50%) 3
    HAEMOGLOBIN DECREASED 0/3 (0%) 0 1/3 (33.3%) 1 0/7 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 2 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    INTERNATIONAL NORMALISED RATIO INCREASED 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    NEUTROPHIL COUNT DECREASED 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/4 (25%) 1 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    PLATELET COUNT DECREASED 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 8 0/4 (0%) 0 1/8 (12.5%) 4 0/3 (0%) 0 0/2 (0%) 0
    WEIGHT DECREASED 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 2 0/6 (0%) 0 1/7 (14.3%) 1 1/4 (25%) 2 1/8 (12.5%) 1 0/3 (0%) 0 0/2 (0%) 0
    WEIGHT INCREASED 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    WHITE BLOOD CELL COUNT INCREASED 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 0/2 (0%) 0
    Metabolism and nutrition disorders
    DECREASED APPETITE 1/3 (33.3%) 1 2/3 (66.7%) 2 3/7 (42.9%) 4 3/6 (50%) 4 2/7 (28.6%) 2 4/4 (100%) 4 1/8 (12.5%) 1 0/3 (0%) 0 0/2 (0%) 0
    DEHYDRATION 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 2/8 (25%) 3 0/3 (0%) 0 0/2 (0%) 0
    DIABETES MELLITUS INADEQUATE CONTROL 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    HYPERCHOLESTEROLAEMIA 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    HYPERKALAEMIA 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    HYPOALBUMINAEMIA 1/3 (33.3%) 1 1/3 (33.3%) 1 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    HYPOCALCAEMIA 1/3 (33.3%) 1 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    HYPOGLYCAEMIA 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/4 (25%) 3 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    HYPOKALAEMIA 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 0/4 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 0/2 (0%) 0
    HYPOMAGNESAEMIA 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 1/4 (25%) 1 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    HYPOPHOSPHATAEMIA 0/3 (0%) 0 1/3 (33.3%) 3 0/7 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 3 0/4 (0%) 0 2/8 (25%) 2 0/3 (0%) 0 0/2 (0%) 0
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 2 1/6 (16.7%) 1 0/7 (0%) 0 1/4 (25%) 1 2/8 (25%) 2 0/3 (0%) 0 1/2 (50%) 1
    BACK PAIN 0/3 (0%) 0 1/3 (33.3%) 1 0/7 (0%) 0 2/6 (33.3%) 2 2/7 (28.6%) 2 2/4 (50%) 2 1/8 (12.5%) 1 0/3 (0%) 0 0/2 (0%) 0
    FIBROMYALGIA 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/4 (25%) 1 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    FLANK PAIN 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 0/2 (0%) 0
    GROIN PAIN 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 1/2 (50%) 1
    LIMB DISCOMFORT 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/4 (25%) 1 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    MUSCLE TIGHTNESS 1/3 (33.3%) 2 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    MUSCULAR WEAKNESS 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/4 (25%) 1 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    MUSCULOSKELETAL CHEST PAIN 1/3 (33.3%) 1 1/3 (33.3%) 1 1/7 (14.3%) 1 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    MUSCULOSKELETAL DISCOMFORT 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    MUSCULOSKELETAL PAIN 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 2 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    MUSCULOSKELETAL STIFFNESS 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    MYALGIA 1/3 (33.3%) 1 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    PAIN IN EXTREMITY 1/3 (33.3%) 2 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 1/4 (25%) 2 1/8 (12.5%) 1 0/3 (0%) 0 0/2 (0%) 0
    SENSATION OF HEAVINESS 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/4 (25%) 1 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    METASTATIC PAIN 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 1/2 (50%) 2
    Nervous system disorders
    DIZZINESS 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 1/7 (14.3%) 1 1/4 (25%) 2 3/8 (37.5%) 8 0/3 (0%) 0 0/2 (0%) 0
    DYSGEUSIA 0/3 (0%) 0 1/3 (33.3%) 1 0/7 (0%) 0 0/6 (0%) 0 2/7 (28.6%) 2 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    HEADACHE 0/3 (0%) 0 1/3 (33.3%) 1 0/7 (0%) 0 2/6 (33.3%) 2 0/7 (0%) 0 1/4 (25%) 1 1/8 (12.5%) 1 0/3 (0%) 0 0/2 (0%) 0
    HYPOGEUSIA 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    HYPOSMIA 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    MEMORY IMPAIRMENT 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 0/2 (0%) 0
    NEURALGIA 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    NEUROPATHY PERIPHERAL 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 1/4 (25%) 1 0/8 (0%) 0 0/3 (0%) 0 1/2 (50%) 1
    PARAESTHESIA 1/3 (33.3%) 3 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    PERIPHERAL SENSORY NEUROPATHY 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 0/2 (0%) 0
    RESTLESS LEGS SYNDROME 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/4 (25%) 1 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    SEDATION 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    TREMOR 1/3 (33.3%) 1 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    Psychiatric disorders
    AGITATION 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    ANXIETY 0/3 (0%) 0 1/3 (33.3%) 1 1/7 (14.3%) 1 1/6 (16.7%) 2 1/7 (14.3%) 1 1/4 (25%) 1 2/8 (25%) 3 0/3 (0%) 0 1/2 (50%) 1
    CONFUSIONAL STATE 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    DEPRESSION 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 2/6 (33.3%) 2 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    FLAT AFFECT 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/4 (25%) 1 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    INSOMNIA 0/3 (0%) 0 1/3 (33.3%) 1 1/7 (14.3%) 1 0/6 (0%) 0 0/7 (0%) 0 2/4 (50%) 2 1/8 (12.5%) 1 0/3 (0%) 0 0/2 (0%) 0
    SLEEP DISORDER 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    Renal and urinary disorders
    BLADDER PAIN 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    CHROMATURIA 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    DYSURIA 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    NOCTURIA 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 0/2 (0%) 0
    POLLAKIURIA 0/3 (0%) 0 1/3 (33.3%) 1 2/7 (28.6%) 2 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    URINARY INCONTINENCE 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/4 (25%) 1 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    URINARY RETENTION 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    Reproductive system and breast disorders
    UTERINE HAEMORRHAGE 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    ATELECTASIS 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    COUGH 1/3 (33.3%) 2 0/3 (0%) 0 1/7 (14.3%) 1 1/6 (16.7%) 1 0/7 (0%) 0 0/4 (0%) 0 2/8 (25%) 3 0/3 (0%) 0 0/2 (0%) 0
    DYSPNOEA 1/3 (33.3%) 3 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 0/2 (0%) 0
    DYSPNOEA EXERTIONAL 1/3 (33.3%) 3 2/3 (66.7%) 3 0/7 (0%) 0 1/6 (16.7%) 1 2/7 (28.6%) 2 0/4 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 0/2 (0%) 0
    EPISTAXIS 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 0/2 (0%) 0
    HAEMOPTYSIS 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    HICCUPS 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/4 (25%) 1 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    NASAL CONGESTION 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/8 (12.5%) 1 1/3 (33.3%) 1 0/2 (0%) 0
    NASAL DRYNESS 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 0/2 (0%) 0
    PLEURAL EFFUSION 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    PRODUCTIVE COUGH 1/3 (33.3%) 1 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    RALES 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    RESPIRATORY TRACT CONGESTION 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 1/3 (33.3%) 1 0/2 (0%) 0
    Skin and subcutaneous tissue disorders
    ALOPECIA 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 1/2 (50%) 1
    COLD SWEAT 0/3 (0%) 0 1/3 (33.3%) 1 0/7 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    DRUG ERUPTION 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    ERYTHEMA 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 1/6 (16.7%) 1 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    HYPERHIDROSIS 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    PETECHIAE 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 1/7 (14.3%) 1 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    PRURITUS 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    PRURITUS GENERALISED 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    RASH 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 2/6 (33.3%) 3 1/7 (14.3%) 3 1/4 (25%) 1 2/8 (25%) 2 0/3 (0%) 0 0/2 (0%) 0
    RASH GENERALISED 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 1/2 (50%) 1
    SKIN EXFOLIATION 1/3 (33.3%) 1 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/4 (25%) 1 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    SKIN LESION 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 2 0/6 (0%) 0 0/7 (0%) 0 1/4 (25%) 1 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    SKIN TIGHTNESS 1/3 (33.3%) 1 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    Vascular disorders
    HOT FLUSH 0/3 (0%) 0 1/3 (33.3%) 1 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/2 (0%) 0
    HYPOTENSION 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/8 (12.5%) 2 0/3 (0%) 0 0/2 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    The investigator agrees to provide to the sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication that report any results of the study.

    Results Point of Contact

    Name/Title Senior Vice President, Global Clinical Development
    Organization Merck Sharp & Dohme Corp.
    Phone 1-800-672-6372
    Email ClinicalTrialsDisclosure@merck.com
    Responsible Party:
    Merck Sharp & Dohme LLC
    ClinicalTrials.gov Identifier:
    NCT00779584
    Other Study ID Numbers:
    • P05248
    • MK-8776-002
    First Posted:
    Oct 24, 2008
    Last Update Posted:
    Aug 27, 2018
    Last Verified:
    Jul 1, 2018