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

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT01405599
• Date of registration: 22/07/2011
• Prospective Registration: No
• Primary sponsor: Norgine
• Public title: Evaluation of the Pharmacokinetics of Ulimorelin in Subjects With Hepatic Impairment and Healthy Subjects
• Scientific title: 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
• Date of first enrolment: June 2011
• Target sample size: 32
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT01405599
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
• Phase: Phase 1

Countries of recruitment

Slovakia

Contacts

• Name: Maria Tomas, PhD
• Affiliation: Norgine

Key inclusion & exclusion criteria

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
a1-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



Age minimum: 18 Years
Age maximum: 75 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Digestive System Disorders

Intervention(s)

Drug: Ulimorelin

Primary Outcome(s)

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]

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]

Secondary ID(s)

NPJ5004-01/2011 (HEP)

Source(s) of Monetary Support

Please refer to primary and secondary sponsors