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

• ClinicalTrials.gov Identifier: NCT01732263
• Recruitment Status: Completed
• First Posted: November 22, 2012
• Results First Posted: May 15, 2014
• Last Update Posted: May 15, 2014
• Sponsor: Shire
• Information provided by (Responsible Party): Shire

Tracking Information

• First Submitted Date: November 19, 2012
• First Posted Date: November 22, 2012
• Results First Submitted Date: April 16, 2014
• Results First Posted Date: May 15, 2014
• Last Update Posted Date: May 15, 2014
• Study Start Date: December 2012
• Actual Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 16, 2014)

• Area Under the Plasma Concentration-time Curve (AUC) of SSP-004184 [ Time Frame: Over 96 hours post-dose ]
  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.
• Maximum Plasma Concentration (Cmax) of SSP-004184 [ Time Frame: Over 96 hours post-dose ]
  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.
• Time of Maximum Plasma Concentration (Tmax) for SSP-004184 [ Time Frame: Over 96 hours post-dose ]
  Tmax is the time after administration of a drug when the maximum plasma concentration in the body is reached.
• Plasma Half-Life (T 1/2) of SSP-004184 [ Time Frame: Over 96 hours post-dose ]
  The time it takes for the blood plasma concentration of a substance to halve.
• Total Body Clearance (CL/F) of SSP-004184 [ Time Frame: Over 96 hours post-dose ]
  The rate at which a drug is removed from the body.
• Volume of Distribution (Vz/F) of SSP-004184 [ Time Frame: Over 96 hours post-dose ]
  The distribution of a medication between plasma and the rest of the body.

Original Primary Outcome Measures (submitted: November 21, 2012)

• Area Under the Plasma Concentration Versus Time Curve (AUC) of SSP-004184 (SPD602) [ Time Frame: Assessed over a 96-hour period from post-dose on Day 1 ]
• Maximum Plasma Concentration (Cmax) of SSP-004184 (SPD602) [ Time Frame: Assessed over a 96-hour period from post-dose on Day 1 ]

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of SSP-004184 (SPD602) in Healthy Adults and Subjects With Impaired Liver Function
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Hepatic Impairment
• Healthy

Intervention

Drug: SSP-004184

All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1

Other Name: SPD602, FBS0701

Study Arms

• 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.
  Intervention: Drug: SSP-004184
• Experimental: SSP-004184 (Child-Pugh B Liver Impaired)
  Intervention: Drug: SSP-004184
• Experimental: SSP-004184 (Child-Pugh C Liver Impaired)
  Intervention: Drug: SSP-004184
• Experimental: SSP-004184 (Matched Healthy Subjects)
  Intervention: Drug: SSP-004184

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 3, 2013): 44
• Original Estimated Enrollment (submitted: November 21, 2012): 48
• Actual Study Completion Date: April 2013
• Actual Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01732263
• Other Study ID Numbers: SPD602-105
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Shire
• Study Sponsor: Shire
• Collaborators: Not Provided

Investigators

• Principal Investigator: Kenneth Lasseter, MD; Clinical Pharmacology of Miami

• PRS Account: Shire
• Verification Date: April 2014