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Evaluation of the Pharmacokinetics of Ulimorelin in Subjects With Hepatic Impairment and Healthy Subjects

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01405599
Recruitment Status : Completed
First Posted : July 29, 2011
Last Update Posted : October 16, 2012
Sponsor:
Information provided by (Responsible Party):
Norgine

Tracking Information
First Submitted Date  ICMJE July 22, 2011
First Posted Date  ICMJE July 29, 2011
Last Update Posted Date October 16, 2012
Study Start Date  ICMJE June 2011
Actual Primary Completion Date October 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 28, 2011)
  • Cmax of ulimorelin [ Time Frame: 15, 30, 45, 60, 75, 90 mins, 2, 4, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 h post-infusion ]
    To evaluate the pharmacokinetics of ulimorelin in subjects with mild, moderate and severe hepatic impairment compared with subjects who have normal hepatic function following a single dose administration of ulimorelin
  • AUC of ulimorelin [ Time Frame: 15, 30, 45, 60, 75, 90 mins, 2, 4, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 h post-infusion ]
    To evaluate the pharmacokinetics of ulimorelin in subjects with mild, moderate and severe hepatic impairment compared with subjects who have normal hepatic function following a single dose administration of ulimorelin
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: July 28, 2011)
  • Adverse events [ Time Frame: 7 days ]
    To evaluate the safety and tolerability of ulimorelin in subjects with hepatic impairment following a single dose administration of ulimorelin
  • Laboratory safety tests [ Time Frame: 7 days ]
    To evaluate the safety and tolerability of ulimorelin in subjects with hepatic impairment following a single dose administration of ulimorelin
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation of the Pharmacokinetics of Ulimorelin in Subjects With Hepatic Impairment and Healthy Subjects
Official Title  ICMJE Evaluation of the Pharmacokinetics, Safety and Tolerability of a Single Dose of Ulimorelin in Subjects With Mild, Moderate and Severe Hepatic Impairment, in Comparison With Healthy Subjects
Brief Summary Evaluation of the effect of hepatic impairment on the pharmacokinetics of ulimorelin after a single intravenous (IV) dose in order to identify potential patients at risks in terms of severity of hepatic dysfunction and to determine whether their dosage should be adjusted.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Digestive System Disorders
Intervention  ICMJE Drug: Ulimorelin
Single dose of 480 micrograms/kg administered as a 30 minute intravenous infusion
Other Name: TZP101
Study Arms  ICMJE
  • Experimental: Control
    Healthy subjects
    Intervention: Drug: Ulimorelin
  • Experimental: Severe hepatic impairment
    CTP class C
    Intervention: Drug: Ulimorelin
  • Experimental: Moderate hepatic impairment
    CTP class B
    Intervention: Drug: Ulimorelin
  • Experimental: Mild hepatic impairment
    CTP class A
    Intervention: Drug: Ulimorelin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 15, 2012)
32
Original Estimated Enrollment  ICMJE
 (submitted: July 28, 2011)
24
Actual Study Completion Date  ICMJE October 2011
Actual Primary Completion Date October 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Main Criteria for Inclusion All Subjects:

  • Adult male or female subjects age 18 to 75 years (both inclusive)
  • Able to understand and willing to sign an informed consent form (ICF) and able to comply with the study restrictions
  • Female subjects must be postmenopausal (for at least 1 year and confirmed by serum follicle-stimulating hormone (FSH) at screening), surgically sterile, practicing true abstinence and/or must be using adequate contraception for the duration of the study (e.g. contraceptive implants, injectables, oral contraceptives, and intra-uterine device and/or barrier methods (condom/occlusive cap with spermicidal foam/gel/film/cream/suppository))
  • Females of childbearing potential must have a negative pregnancy test at screening and Day -1
  • Weight ≥ 50 kg and ≤ 200 kg
  • Body mass index (BMI) ≤ 40.0 kg/m2, where BMI (kg/m2) = Body weight (kg)/Height2 (m2) Inclusion Criteria Hepatic Impairment Subjects (in addition to the criteria for all subjects):
  • Documented mild, moderate or severe hepatic impairment defined as either Child-Pugh A, B or C at screening
  • Stable hepatic impairment, defined as no clinically significant change in disease status within the last 30 days before screening, as documented by the subject's recent medical history (e.g., no worsening of clinical signs of hepatic impairment and no worsening of total bilirubin or prothrombin time by more than 50%)
  • Must be on a stable dose of medication and/or treatment regimen at least 2 weeks before dosing of study medication
  • Subjects with a history of substance abuse may be enrolled provided that they have not abused drugs or alcohol for at least 6 months preceding the study Inclusion Criteria for Healthy Subjects (in addition to criteria for all subjects):
  • Subjects with normal hepatic function, and liver parameters within normal range unless approved by the Sponsor's Medical Representative
  • Subjects not using prescription drugs or non-prescription drugs, including over-the-counter medication, non-routine vitamins and herbal products within 3 weeks prior to dosing of investigational product [use of oral contraceptives, diuretics, noncardioselective beta-blockers, topically applied medication (eye-/nose-drops and creams) and occasional use of metaclopramide, ibuprofen and paracetamol is permitted]. Use of any other medication has to be discussed and agreed before inclusion of the subject with the Medical Monitor and the Sponsor's medical representative

Exclusion Criteria:

Criteria for Exclusion All Subjects:

  • Known or suspected allergy to the trial product or related products
  • History of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reaction
  • Participation in another investigational drug trial within 30 days prior to dosing (or 5 times the half life of the drug if longer)
  • Acute illness within 14 days prior to dosing unless mild in severity and approved by the Investigator and Sponsor's medical representative
  • History of drug abuse or positive urine drug screen (if not due to concomitant medication) at Screening and/or Day -1
  • Ingestion of alcohol and caffeine within 24 hours prior to dosing and for the duration of the study
  • Donation of more than 450mL of blood / blood products in the 30 days prior to dosing, and/or blood donation in the 30 days prior to dosing
  • Positive result to the screening test for HIV-1 antibodies, HIV-2 antibodies or HIV-1 antigen according to locally used diagnostic testing
  • Creatinine clearance <50mL/minute, estimated using serum creatinine with the formula [(140 - age in years) × weight in kg]/[(72 × serum creatinine in mg/dL) × 0.85 for female subjects]
  • Consumption of Seville oranges, grapefruit or grapefruit juice, star fruit and exotic fruits from 7 days prior to first dose of study medication and for entire duration of the study
  • Clinically significant abnormal haematology, biochemistry, coagulation or urinalysis screening tests, as judged by the Investigator other than the abnormal values expected considering the underlying disease
  • Subject with any disease or condition which the Investigator feels would interfere with the trial outcome or compliance except for conditions associated with hepatic impairment in the group of subjects with compromised hepatic function
  • Uncontrolled treated/untreated hypertension (systolic blood pressure ≥ 160 mmHg and /or diastolic blood pressure ≥ 105 mmHg)
  • Use of prescription or over-the-counter medication that is extensively bound to α1-acid glycoprotein (AAG) which the Investigator or Sponsor feels would interfere with the trial outcome
  • History of cancer (judged not to be in full remission) or presence of cancer (except basal cell skin cancer or squamous cell skin cancer) as judged by the Investigator
  • Subject who has undergone liver transplantation
  • Not able or willing to refrain from smoking during the inpatient period
  • Any condition that would make the subject unsuitable for clinical trial participation as judged by the Investigator

Exclusion Criteria Hepatic Impairment Subjects (in addition to criteria for all subjects):

  • Any medical or surgical conditions, excluding underlying liver disease, which may significantly interfere with the pharmacokinetics of the study drug
  • Fluctuating or rapidly deteriorating hepatic function

Exclusion Criteria for Healthy Subjects (in addition to criteria for all subjects):

  • Subjects with clinically significant illness as judged by the Investigator
  • Exposure to more than three new chemical entities within 12 months prior to the first dosing day
  • Known acute hepatitis with viral, alcoholic, toxic or autoimmunological aetiology within the last 6 months. Positive result to the screening test for Hepatitis B antigen or Hepatitis C antibodies according to locally used diagnostic testing
  • Strenuous exercise within 48 hours prior to dosing and for the duration of the study
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Slovakia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01405599
Other Study ID Numbers  ICMJE NPJ5004-01/2011 (HEP)
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Norgine
Study Sponsor  ICMJE Norgine
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Maria Tomas, PhD Norgine
PRS Account Norgine
Verification Date October 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP