Study of SSP-004184 (SPD602) in Healthy Adults and Subjects With Impaired Liver Function

A Phase 1, Open-label, Single-dose Study of the Pharmacokinetics, Safety, and Tolerability of SSP-004184 (SPD602) in Subjects With Hepatic Impairment Compared to Matched Healthy Subjects

The purpose of this study is to evaluate how much of the study drug SSP-004184 (SPD602) is absorbed by the body and how long it takes to be eliminated from the body in healthy subjects and subjects with mild, moderate, and severe hepatic (liver) impairment compared with subjects with healthy normal liver function.

Study Overview

• Status: Completed
• Conditions: Healthy; Hepatic Impairment
• Intervention / Treatment: Drug: SSP-004184

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33014
      • Clinical Pharmacology of Miami
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center (OCRC)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18-65 years inclusive at the time of consent.
• Willingness to comply with any applicable contraceptive requirements of the protocol and is:
• Male, or
• Non pregnant, non lactating female
• Females must be at least 90 days post partum or nulliparous.

Subjects who do not have hepatic impairment (healthy subjects)

• Normal renal function.

Subjects with hepatic impairment

• Subjects must provide a letter of evaluation from a hepatologist or copy of supporting documents confirming the subject's hepatic impairment (a liver biopsy is preferable but not mandatory).
• Hepatic impairment should be primary and must not be a complication of an underlying primary systemic disease (eg, patients with metastatic cancer and cancer cachexia)
• Documented chronic stable liver impairment

Exclusion Criteria

Subjects who do not have hepatic impairment (healthy subjects)

• A positive HIV antibody screen, Hepatitis B surface antigen, or Hepatitis C virus antibody screen.

Subjects with hepatic impairment

• Presence of a hepatocellular carcinoma, or an acute hepatic disease caused by an infection or drug toxicity.
• Presence of surgically created or transjugular intrahepatic portal systemic shunts.
• A positive HIV antibody screen.
• Renal insufficiency.

All subjects

• Subject has a history of thyroid disorder.
• History of nephrotic syndrome.
• History of alcohol or other substance abuse within the last year.
• A positive screen for alcohol or drugs of abuse.
• Male subjects who consume more than 3 units of alcohol per day. Female subjects who consume more than 2 units of alcohol per day. (1 alcohol unit = 1 beer [12 oz/355 mL] = 1 wine [5 oz/150 mL] = 1 liquor [1.5 oz/40 mL] = 0.75 oz/20 mL alcohol.)
• Caffeine consumption: For healthy subjects: Routine consumption of more than 2 units of caffeine per day or subjects who experience caffeine withdrawal headaches or have a history of caffeine withdrawal headaches. (One caffeine unit is contained in the following items: one 6 oz/180 mL cup of coffee, two 12 oz/355 mL (ie, 24 oz/710 mL cola) cans of cola, one 12 oz/355 mL cup of tea, three 1 oz/28 g chocolate bars (ie, 3 oz/85 g chocolate). Decaffeinated coffee, tea, or cola are not considered to contain caffeine.)
• Donation of blood or blood products within 60 days.
• Substantial changes in eating habits within 30 days.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SSP-004184 (Child-Pugh A Liver Impaired); The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.	Drug: SSP-004184; All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1; Other Names: SPD602, FBS0701
Experimental: SSP-004184 (Child-Pugh B Liver Impaired)	Drug: SSP-004184; All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1; Other Names: SPD602, FBS0701
Experimental: SSP-004184 (Child-Pugh C Liver Impaired)	Drug: SSP-004184; All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1; Other Names: SPD602, FBS0701
Experimental: SSP-004184 (Matched Healthy Subjects)	Drug: SSP-004184; All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1; Other Names: SPD602, FBS0701

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Concentration-time Curve (AUC) of SSP-004184	AUC can be used as a measure of drug exposure. It is derived from drug concentration and time so it gives a measure how much and how long a drug stays in a body.	Over 96 hours post-dose
Maximum Plasma Concentration (Cmax) of SSP-004184	Cmax is a term that refers to the maximum (or peak) concentration that a drug achieves in the body after the drug has been administrated.	Over 96 hours post-dose
Time of Maximum Plasma Concentration (Tmax) for SSP-004184	Tmax is the time after administration of a drug when the maximum plasma concentration in the body is reached.	Over 96 hours post-dose
Plasma Half-Life (T 1/2) of SSP-004184	The time it takes for the blood plasma concentration of a substance to halve.	Over 96 hours post-dose
Total Body Clearance (CL/F) of SSP-004184	The rate at which a drug is removed from the body.	Over 96 hours post-dose
Volume of Distribution (Vz/F) of SSP-004184	The distribution of a medication between plasma and the rest of the body.	Over 96 hours post-dose

Collaborators and Investigators

• Sponsor: Shire

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2012
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: November 19, 2012
• First Submitted That Met QC Criteria: November 21, 2012
• First Posted (Estimate): November 22, 2012

Study Record Updates

• Last Update Posted (Actual): July 19, 2021
• Last Update Submitted That Met QC Criteria: June 22, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: SPD602-105