Trial Outcomes & Findings for Bioavailability Study for New Atorvastatin Formulation (NCT NCT00844376)

Results Overview

Geometric means of AUC48 = area under the plasma concentration-time profile from time zero (0) to 48 hours postdose of atorvastatin (test versus \[vs\] reference); measured in nanograms times hour per milliliter (ng.hr/mL).

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

12 participants

Primary outcome timeframe

5 days

Results posted on

2021-03-10

Participant Flow

One center in the U.S.

This study contained two sequences of 6 subjects per sequence. Each sequence received either test treatment followed by reference treatment, or reference treatment followed by test treatment. The order of administration was randomized to either of 2 sequences.

Participant milestones

Participant milestones
Measure	Test Drug First (Atorvastatin EP Suspension) 80-milligram (mg) Extemporaneous preparation (EP) suspension atorvastatin prototype formulation as a single dose in the first intervention period and commercial (reference) 80 mg atorvastatin tablet (Lipitor®) as a single dose in the second intervention period. Period 2 began immediately after period 1.	Reference Drug First (Atorvastatin Tablet) 80-mg Commercial atorvastatin tablet (Lipitor®) as a single dose in the first intervention period and 80-mg EP suspension atorvastatin prototype formulation as a single dose in the second intervention period. Period 2 began immediately after period 1.
Period 1: First Intervention STARTED	6	6
Period 1: First Intervention COMPLETED	5	6
Period 1: First Intervention NOT COMPLETED	1	0
Period 2: Second Intervention STARTED	5	6
Period 2: Second Intervention COMPLETED	5	6
Period 2: Second Intervention NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Test Drug First (Atorvastatin EP Suspension) 80-milligram (mg) Extemporaneous preparation (EP) suspension atorvastatin prototype formulation as a single dose in the first intervention period and commercial (reference) 80 mg atorvastatin tablet (Lipitor®) as a single dose in the second intervention period. Period 2 began immediately after period 1.	Reference Drug First (Atorvastatin Tablet) 80-mg Commercial atorvastatin tablet (Lipitor®) as a single dose in the first intervention period and 80-mg EP suspension atorvastatin prototype formulation as a single dose in the second intervention period. Period 2 began immediately after period 1.
Period 1: First Intervention Withdrawal by Subject	1	0

Baseline Characteristics

Bioavailability Study for New Atorvastatin Formulation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Participants n=12 Participants
Age, Continuous	34.8 years STANDARD_DEVIATION 7.7 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants

PRIMARY outcome

Timeframe: 5 days

Geometric means of AUC48 = area under the plasma concentration-time profile from time zero (0) to 48 hours postdose of atorvastatin (test versus \[vs\] reference); measured in nanograms times hour per milliliter (ng.hr/mL).

Outcome measures

Outcome measures
Measure	Test n=12 Participants 80-mg Extemporaneous preparation suspension Atorvastatin prototype formulation	Reference n=11 Participants 80-mg Commercial atorvastatin tablet (Lipitor®)
Area Under the Curve From Predose (Time Zero) to 48 Hours Post-dose (AUC48)	135.05 ng.h/mL Interval 52.5 to 233.0	140.79 ng.h/mL Interval 64.1 to 243.0

PRIMARY outcome

Timeframe: 5 days

Geometric means of AUC infinity (AUCinf) = area under the plasma concentration-time curve from time zero (0) extrapolated to infinite time; measured in ng.hr/mL of atorvastatin (test vs reference).

Outcome measures

Outcome measures
Measure	Test n=12 Participants 80-mg Extemporaneous preparation suspension Atorvastatin prototype formulation	Reference n=11 Participants 80-mg Commercial atorvastatin tablet (Lipitor®)
Area Under the Curve From Predose (Time Zero) to Extrapolated Infinite Time (AUC Infinity)	135.88 ng.hr/mL Interval 51.2 to 234.0	142.86 ng.hr/mL Interval 65.0 to 247.0

PRIMARY outcome

Timeframe: 5 days

Geometric mean of Cmax = maximum observed plasma concentration of atorvastatin (test vs reference); measured in nanograms per milliliter (ng/mL).

Outcome measures

Outcome measures
Measure	Test n=12 Participants 80-mg Extemporaneous preparation suspension Atorvastatin prototype formulation	Reference n=11 Participants 80-mg Commercial atorvastatin tablet (Lipitor®)
Maximum Observed Plasma Concentration (Cmax)	38.74 ng/mL Interval 20.3 to 86.8	33.24 ng/mL Interval 16.6 to 52.2

SECONDARY outcome

Timeframe: 5 days

Geometric mean of AUClast = area under the plasma concentration-time curve from time zero (0) to the last measurable concentration of atorvastatin (test vs reference); measured as ng.hr/mL

Outcome measures

Outcome measures
Measure	Test n=12 Participants 80-mg Extemporaneous preparation suspension Atorvastatin prototype formulation	Reference n=11 Participants 80-mg Commercial atorvastatin tablet (Lipitor®)
Area Under the Curve From Predose (Time Zero) to Last Quantifiable Concentration (AUClast)	130.21 ng.hr/mL Interval 45.5 to 231.0	137.49 ng.hr/mL Interval 56.0 to 243.0

SECONDARY outcome

Timeframe: 5 days

Geometric mean of Kel= termination phase rate constant for atorvastatin (test vs reference); measured as 1 per hour (1/hr).

Outcome measures

Outcome measures
Measure	Test n=12 Participants 80-mg Extemporaneous preparation suspension Atorvastatin prototype formulation	Reference n=11 Participants 80-mg Commercial atorvastatin tablet (Lipitor®)
Terminal Phase Rate Constant (Kel)	0.12 1/hr Interval 0.09 to 0.26	0.10 1/hr Interval 0.06 to 0.15

SECONDARY outcome

Timeframe: 5 days

Median of Tmax = time to maximum plasma concentration (Cmax) (test vs reference); measured in hours (hr).

Outcome measures

Outcome measures
Measure	Test n=12 Participants 80-mg Extemporaneous preparation suspension Atorvastatin prototype formulation	Reference n=11 Participants 80-mg Commercial atorvastatin tablet (Lipitor®)
Time to Reach Maximum Plasma Concentration (Tmax)	0.52 hr Interval 0.5 to 2.0	0.50 hr Interval 0.5 to 3.0

SECONDARY outcome

Timeframe: 5 days

Mean of t1/2 = terminal elimination half-life of atorvastatin (test vs reference); measured in hours.

Outcome measures

Outcome measures
Measure	Test n=12 Participants 80-mg Extemporaneous preparation suspension Atorvastatin prototype formulation	Reference n=11 Participants 80-mg Commercial atorvastatin tablet (Lipitor®)
Plasma Elimination Half-life (t1/2)	5.95 hr Standard Deviation 1.40	7.21 hr Standard Deviation 2.23

Adverse Events

Test

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Reference

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Test n=12 participants at risk 80-mg Extemporaneous preparation suspension Atorvastatin prototype formulation	Reference n=11 participants at risk 80-mg Commercial atorvastatin tablet (Lipitor®)
Nervous system disorders headache	8.3% 1/12	9.1% 1/11

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of \< 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), \< 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