Trial Outcomes & Findings for Study To Evaluate Pharmacokinetics Of Sirolimus In Stable Renal Transplant Recipients (NCT NCT01236378)

NCT ID: NCT01236378

Last Updated: 2012-03-01

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 24 participants
• Primary outcome timeframe: Predose (0 hour) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and 24 hours post dose
• Results posted on: 2012-03-01

Participant Flow

Participant milestones

Measure	Sirolimus Sirolimus, 1 milligram (mg) tablet formulation; total daily dosage could have varied from participant to participant, dosage must have been stable for at least 2 weeks prior to screening and continued with no change until completion of the last pharmacokinetic (PK) sample collection.
Overall Study STARTED	24
Overall Study COMPLETED	24
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study To Evaluate Pharmacokinetics Of Sirolimus In Stable Renal Transplant Recipients

Baseline characteristics by cohort

Measure	Sirolimus n=24 Participants Sirolimus, 1 mg tablet formulation; total daily dosage could have varied from participant to participant, dosage must have been stable for at least 2 weeks prior to screening and continued with no change until completion of the last PK sample collection.
Age, Customized 18 to 44 years	16 participants n=5 Participants
Age, Customized 45 to 64 years	8 participants n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	21 Participants n=5 Participants

PRIMARY outcome

Timeframe: Predose (0 hour) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and 24 hours post dose

Population: PK parameter analysis population: All treated participants who had at least 1 of the PK parameters of primary interest.

Outcome measures

Measure	Sirolimus n=24 Participants Sirolimus, 1 mg tablet formulation; total daily dosage could have varied from participant to participant, dosage must have been stable for at least 2 weeks prior to screening and continued with no change until completion of the last PK sample collection.
Maximum Observed Blood Concentration at Steady State (Cmax,ss)	14.07 nanogram per milliliter (ng/mL) Standard Deviation 13.433

PRIMARY outcome

Timeframe: Predose (0 hour) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and 24 hours post dose

Population: PK Parameter Analysis Population

Outcome measures

Measure	Sirolimus n=24 Participants Sirolimus, 1 mg tablet formulation; total daily dosage could have varied from participant to participant, dosage must have been stable for at least 2 weeks prior to screening and continued with no change until completion of the last PK sample collection.
Time to Reach Maximum Observed Blood Concentration at Steady State (Tmax,ss)	2.49 hours Interval 0.983 to 12.0

PRIMARY outcome

Timeframe: Predose (0 hour) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and 24 hours post dose

Population: PK Parameter Analysis Population

Outcome measures

Measure	Sirolimus n=24 Participants Sirolimus, 1 mg tablet formulation; total daily dosage could have varied from participant to participant, dosage must have been stable for at least 2 weeks prior to screening and continued with no change until completion of the last PK sample collection.
Observed Blood Trough Concentration at Steady State (Ctrough,ss)	5.906 ng/mL Standard Deviation 6.2621

PRIMARY outcome

Timeframe: Predose (0 hour) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and 24 hours post dose

Population: PK Parameter Analysis Population

Outcome measures

Measure	Sirolimus n=24 Participants Sirolimus, 1 mg tablet formulation; total daily dosage could have varied from participant to participant, dosage must have been stable for at least 2 weeks prior to screening and continued with no change until completion of the last PK sample collection.
Average Blood Concentration at Steady State (Cave,ss)	8.297 ng/mL Standard Deviation 8.7384

PRIMARY outcome

Timeframe: Predose (0 hour) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and 24 hours post dose

Population: PK Parameter Analysis Population

Outcome measures

Measure	Sirolimus n=24 Participants Sirolimus, 1 mg tablet formulation; total daily dosage could have varied from participant to participant, dosage must have been stable for at least 2 weeks prior to screening and continued with no change until completion of the last PK sample collection.
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) at Steady State	199.3 nanogram hour per milliliter (ng*h/mL) Standard Deviation 209.96

PRIMARY outcome

Timeframe: Predose (0 hour) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and 24 hours post dose

Population: PK Parameter Analysis Population

DF, also known as peak to trough fluctuation (PTF) (calculated as [Cmax minus Ctrough] divided by Cave), is a unit-less ratio of the Cmax to Ctrough decrease expressed as a fraction of the average concentration during a dosing interval.

Outcome measures

Measure	Sirolimus n=24 Participants Sirolimus, 1 mg tablet formulation; total daily dosage could have varied from participant to participant, dosage must have been stable for at least 2 weeks prior to screening and continued with no change until completion of the last PK sample collection.
Degree of Fluctuation (DF)	1.064 ratio Standard Deviation 0.3226

PRIMARY outcome

Timeframe: Predose (0 hour) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and 24 hours post dose

Population: PK Parameter Analysis Population

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.

Outcome measures

Measure	Sirolimus n=24 Participants Sirolimus, 1 mg tablet formulation; total daily dosage could have varied from participant to participant, dosage must have been stable for at least 2 weeks prior to screening and continued with no change until completion of the last PK sample collection.
Apparent Oral Clearance (CL/F)	10.14 liter per hour (L/h) Standard Deviation 4.3678

SECONDARY outcome

Timeframe: From baseline up to Day 4

Population: All participants.

Serum creatinine, an indicator of kidney function, formed from the metabolism of creatine, commonly found in blood, urine, and muscle tissue, is removed from blood by kidneys and excreted in urine. Increased creatinine in blood indicates decreased kidney function. Creatinine levels are age, gender and race dependent as they are related to an individual's muscle mass. Renal transplant recipients may have elevated serum creatinine. For this study an abnormal serum creatinine level is defined as 1.3 times the upper limit of normal (ULN) for the laboratory where the determination was performed.

Outcome measures

Measure	Sirolimus n=24 Participants Sirolimus, 1 mg tablet formulation; total daily dosage could have varied from participant to participant, dosage must have been stable for at least 2 weeks prior to screening and continued with no change until completion of the last PK sample collection.
Number of Participants With Serum Creatinine Levels More Than (>) 1.3 Times the Upper Limit of Normal Baseline	5 participants
Number of Participants With Serum Creatinine Levels More Than (>) 1.3 Times the Upper Limit of Normal Day 4	4 participants

SECONDARY outcome

Timeframe: From baseline up to Day 4

Population: All participants.

GFR, an index of kidney function, describes flow rate of filtered fluid through the kidney. GFR can be measured directly or estimated using established formulas. GFR was calculated using the Simplified Modification of Diet in Renal Dysfunction (MDRD) GFR equation. Normal GFR is >90 mL/min/1.73 m^2; children and older people usually have lower GFR. Often, kidney transplant recipients do not have normal GFRs. Lower values indicate poor kidney function. GFR <15 mL/min/1.73 m^2 is consistent with kidney failure. For this posting, the number of subjects with a GFR <60 mL/min/1.73 m^2 is listed.

Outcome measures

Measure	Sirolimus n=24 Participants Sirolimus, 1 mg tablet formulation; total daily dosage could have varied from participant to participant, dosage must have been stable for at least 2 weeks prior to screening and continued with no change until completion of the last PK sample collection.
Number of Participants With Estimated Glomerular Filtration Rate (GFR) Less Than (<) 60 mL/Min/1.73 m^2 Baseline	7 participants
Number of Participants With Estimated Glomerular Filtration Rate (GFR) Less Than (<) 60 mL/Min/1.73 m^2 Day 4	7 participants

Adverse Events

Sirolimus

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: ClinicalTrials.gov_Inquiries@pfizer.com

Results disclosure agreements

• Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
• Publication restrictions are in place

Restriction type: OTHER