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

NCT01405599 | Completed Phase 1 DMC

• 1 other identifier: NPJ5004-01/2011 (HEP)
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Digestive System Disorders

Keywords

Ulimorelin; Hepatic Impairment

Outcome Measures

Primary Outcomes (2)

• Cmax of ulimorelin

  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

  15, 30, 45, 60, 75, 90 mins, 2, 4, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 h post-infusion

• AUC of ulimorelin

  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

  15, 30, 45, 60, 75, 90 mins, 2, 4, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 h post-infusion

Study Arms (4)

Control

EXPERIMENTAL

Healthy subjects

Drug: Ulimorelin

Severe hepatic impairment

EXPERIMENTAL

CTP class C

Drug: Ulimorelin

Moderate hepatic impairment

EXPERIMENTAL

CTP class B

Drug: Ulimorelin

Mild hepatic impairment

EXPERIMENTAL

CTP class A

Drug: Ulimorelin

Interventions

Ulimorelin DRUG

Single dose of 480 micrograms/kg administered as a 30 minute intravenous infusion

Also known as: TZP101

Control; Mild hepatic impairment; Moderate hepatic impairment; Severe hepatic impairment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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 normal hepatic function, and liver parameters within normal range unless approved by the Sponsor's Medical Representative

You may not qualify if:

• 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

Sponsors & Collaborators

• Norgine: lead

Study Sites (1)

Univerzitna nemocnica Bratislava, nem.

Bratislava, 83305, Slovakia

Location

MeSH Terms

Conditions

Digestive System Diseases

Interventions

ulimorelin

Study Officials

• Maria Tomas, PhD

  Norgine

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: July 22, 2011
• First Posted: July 29, 2011
• Study Start: June 1, 2011
• Primary Completion: October 1, 2011
• Study Completion: October 1, 2011
• Last Updated: October 16, 2012

Record last verified: 2012-10

Locations

SL (1)