Hepatitis, Chronic, Hepatitis C Virus
Conditions
Brief summary
Phase 1 study in HVC (Hepatitis C Virus) infected subjects to determine pharmacokinetics, safety and efficacy in subjects with no or inadequate response to prior treatment.
Interventions
DRUGSmall Molecule Agent (PF-868554)
Study drug will be administered 700mg BID in the fed state for three days.
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
HCV Positive With HCV RNA\>100,000 iu/ml Genotype 1; COHORT A- non responders or partial
Exclusion criteria
HIV HBV co-infection Decompensated liver disease Liver disease due to causes other than HCV, AFP\>200ng/ml
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 11 (Cohort A): Full Analysis Set | Baseline, Day 11 | Plasma HCV RNA levels were quantified using the Abbott RealTime HCV assay (lower limit of quantification \[LLOQ\] = 12 international unit per milliliter \[IU/mL\]). Baseline value calculated as an average of screening, Day 0 and Day 1 (0 hour) measurements. Change from baseline in plasma log10 HCV RNA was calculated for all participants after the last day of dosing (Day 11 for Cohort A). |
| Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 11 (Cohort A): Modified Analysis Set | Baseline, Day 11 | Plasma HCV RNA levels were quantified using the Abbott RealTime HCV assay (LLOQ = 12 IU/mL). Baseline value calculated as an average of screening, Day 0 and Day 1 (0 hour) measurements. Change from baseline in plasma log10 HCV RNA was calculated for all participants after the last day of dosing (Day 11 for Cohort A). |
| Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 4 (Cohort B): Full Analysis Set | Baseline, Day 4 | Plasma HCV RNA levels were quantified using the Abbott RealTime HCV assay (LLOQ = 12 IU/mL). Baseline value calculated as an average of screening, Day 0 and Day 1 (0 hour) measurements. Change from baseline in plasma log10 HCV RNA was calculated for all participants after the last day of dosing (Day 4 for Cohort B). |
| Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 4 (Cohort B): Modified Analysis Set | Baseline, Day 4 | Plasma HCV RNA levels were quantified using the Abbott RealTime HCV assay (LLOQ = 12 IU/mL). Baseline value calculated as the average of screening, Day 0 and Day 1 (0 hour) measurements. Change from baseline in plasma log10 HCV RNA was calculated for all participants after the last day of dosing (Day 4 for Cohort B). |
| Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Nadir: Full Analysis Set | Baseline, Nadir (lowest HCV RNA level), assessed up to Day 11 for Cohort A and Day 4 for Cohort B | Plasma HCV RNA levels were quantified using the Abbott RealTime HCV assay (LLOQ = 12 IU/mL). Change from baseline in plasma Log10 HCV RNA at nadir signified the maximum change observed during the study. |
| Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Nadir: Modified Analysis Set | Baseline, Nadir (lowest HCV RNA level), assessed up to Day 11 for Cohort A and Day 4 for Cohort B | Plasma HCV RNA levels were quantified using the Abbott RealTime HCV assay (LLOQ = 12 IU/mL). Change from baseline in plasma Log10 HCV RNA at nadir signified the maximum change observed during the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) | Predose, 0.5, 1, 2, 6, 8, 12 hours (hrs) postdose on Day 1 for Cohort A and B, pre-evening dose, 0.5, 1, 2, 4, 6, 8, 12 hrs post-evening dose on Day 3 for Cohort B, predose, 0.5, 1, 2, 4, 8, 12 hrs postdose on Day 10 for Cohort A | Area under the concentration curve from time 0 to end of dosing interval (AUCtau), where dosing interval was 12 hours. AUCtau was evaluated at first dose on Day 1 for Cohort A and B, and at last dose for Cohort A (Day 10) and Cohort B (Day 3). |
| Plasma Decay Half-Life (t1/2) | Pre-morning dose, pre-evening dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hrs post-evening dose on Day 3 for Cohort B, predose,0.5, 1, 2, 4, 8, 12, 24, 48 hrs postdose on Day 10 for Cohort A | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. Half-life was evaluated at last dose for Cohort A (Day 10) and Cohort B (Day 3). |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | Predose, 0.5, 1, 2, 6, 8, 12, 14 hrs postdose on Day 1 for Cohort A, B, pre-morning dose, pre-evening dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hrs post-evening dose on Day 3 for Cohort B, predose,0.5, 1, 2, 4, 8, 12, 24, 48 hrs postdose on Day 10 for Cohort A | Area under the serum concentration time-curve from zero to the last measured concentration (AUClast). AUClast was evaluated at first dose on Day 1 for Cohort A and B, and at last dose for Cohort A (Day 10) and Cohort B (Day 3). |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] | Pre-morning dose, pre-evening dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hrs post-evening dose on Day 3 for Cohort B, predose,0.5, 1, 2, 4, 8, 12, 24, 48 hrs postdose on Day 10 for Cohort A | AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞). AUC (0 - ∞) was evaluated at last dose for Cohort A (Day 10) and Cohort B (Day 3). |
| Plasma Concentration at The End of Dosing Interval (Ctau) | Predose, 0.5, 1, 2, 6, 8, 12 hours (hrs) postdose on Day 1 for Cohort A and B, pre-evening dose, 0.5, 1, 2, 4, 6, 8, 12 hrs post-evening dose on Day 3 for Cohort B, predose, 0.5, 1, 2, 4, 8, 12 hrs postdose on Day 10 for Cohort A | Ctau was evaluated at first dose on Day 1 for Cohort A and B, and at last dose for Cohort A (Day 10) and Cohort B (Day 3). |
| Maximum Observed Plasma Concentration (Cmax) | Predose, 0.5, 1, 2, 6, 8, 12, 14 hrs postdose on Day 1 for Cohort A, B, pre-morning dose, pre-evening dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hrs post-evening dose on Day 3 for Cohort B, predose,0.5, 1, 2, 4, 8, 12, 24, 48 hrs postdose on Day 10 for Cohort A | Cmax was evaluated at first dose on Day 1 for Cohort A and B, and at last dose for Cohort A (Day 10) and Cohort B (Day 3). |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | Predose, 0.5, 1, 2, 6, 8, 12, 14 hrs postdose on Day 1 for Cohort A, B, pre-morning dose, pre-evening dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hrs post-evening dose on Day 3 for Cohort B, predose,0.5, 1, 2, 4, 8, 12, 24, 48 hrs postdose on Day 10 for Cohort A | Tmax was evaluated at first dose on Day 1 for Cohort A and B, and at last dose for Cohort A (Day 10) and Cohort B (Day 3). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PF-00868554 450 mg (Cohort A) Participants who had a history of unsuccessful treatment for hepatitis C virus (HCV) with an interferon-alpha (IFN-alpha) regimen (with or without ribavirin \[RBV\]) due to lack of response or relapse, received PF-00868554 450 milligram (mg) tablet orally twice daily, every 12 hours from Day 1 morning dose to Day 10 morning dose in a fasted state. | 10 |
| PF-00868554 700 mg (Cohort B) Participants who did not receive any prior treatment for HCV with an IFN-alpha regimen (with or without RBV) or who discontinued from an IFN-alpha regimen (with or without RBV) after less than or equal to (\<=) 2 weeks of treatment due to tolerability issues or other reasons, received PF-00868554 700 mg tablet orally twice daily, every 12 hours from Day 1 morning dose to Day 3 evening dose in a fed state. | 10 |
| Total | 20 |
Baseline characteristics
| Characteristic | PF-00868554 450 mg (Cohort A) | PF-00868554 700 mg (Cohort B) | Total |
|---|---|---|---|
| Age, Customized 18 to 44 years | 1 participants | 2 participants | 3 participants |
| Age, Customized 45 to 64 years | 9 participants | 7 participants | 16 participants |
| Age, Customized greater than or equal to (>=) 65 years | 0 participants | 1 participants | 1 participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 8 Participants | 9 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 10 | 7 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 |
Outcome results
Primary
Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 11 (Cohort A): Full Analysis Set
Plasma HCV RNA levels were quantified using the Abbott RealTime HCV assay (lower limit of quantification \[LLOQ\] = 12 international unit per milliliter \[IU/mL\]). Baseline value calculated as an average of screening, Day 0 and Day 1 (0 hour) measurements. Change from baseline in plasma log10 HCV RNA was calculated for all participants after the last day of dosing (Day 11 for Cohort A).
Time frame: Baseline, Day 11
Population: Full Analysis Set (FAS) included all randomized participants who took at least 1 dose of study medication and had both baseline and at least 1 valid post-baseline endpoint measurements for HCV viral load.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-00868554 450 mg (Cohort A) | Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 11 (Cohort A): Full Analysis Set | Baseline | 6.11 log10 IU/mL | Standard Deviation 0.449 |
| PF-00868554 450 mg (Cohort A) | Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 11 (Cohort A): Full Analysis Set | Change at Day 11 | -0.45 log10 IU/mL | Standard Deviation 0.439 |
Primary
Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 11 (Cohort A): Modified Analysis Set
Plasma HCV RNA levels were quantified using the Abbott RealTime HCV assay (LLOQ = 12 IU/mL). Baseline value calculated as an average of screening, Day 0 and Day 1 (0 hour) measurements. Change from baseline in plasma log10 HCV RNA was calculated for all participants after the last day of dosing (Day 11 for Cohort A).
Time frame: Baseline, Day 11
Population: Modified Analysis Set (MAS): a subset of FAS which included all participants who had received complete dosage in the corresponding treatment regimen.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-00868554 450 mg (Cohort A) | Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 11 (Cohort A): Modified Analysis Set | Baseline | 6.11 log10 IU/mL | Standard Deviation 0.449 |
| PF-00868554 450 mg (Cohort A) | Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 11 (Cohort A): Modified Analysis Set | Change at Day 11 | -0.45 log10 IU/mL | Standard Deviation 0.439 |
Primary
Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 4 (Cohort B): Full Analysis Set
Plasma HCV RNA levels were quantified using the Abbott RealTime HCV assay (LLOQ = 12 IU/mL). Baseline value calculated as an average of screening, Day 0 and Day 1 (0 hour) measurements. Change from baseline in plasma log10 HCV RNA was calculated for all participants after the last day of dosing (Day 4 for Cohort B).
Time frame: Baseline, Day 4
Population: FAS included all randomized participants who took at least 1 dose of study medication and had both baseline and at least 1 valid post-baseline endpoint measurements for HCV viral load.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-00868554 450 mg (Cohort A) | Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 4 (Cohort B): Full Analysis Set | Baseline | 6.39 log10 IU/mL | Standard Deviation 0.455 |
| PF-00868554 450 mg (Cohort A) | Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 4 (Cohort B): Full Analysis Set | Change at Day 4 | -2.15 log10 IU/mL | Standard Deviation 0.252 |
Primary
Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 4 (Cohort B): Modified Analysis Set
Plasma HCV RNA levels were quantified using the Abbott RealTime HCV assay (LLOQ = 12 IU/mL). Baseline value calculated as the average of screening, Day 0 and Day 1 (0 hour) measurements. Change from baseline in plasma log10 HCV RNA was calculated for all participants after the last day of dosing (Day 4 for Cohort B).
Time frame: Baseline, Day 4
Population: MAS: a subset of FAS which included all participants who had received complete dosage in the corresponding treatment regimen.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-00868554 450 mg (Cohort A) | Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 4 (Cohort B): Modified Analysis Set | Baseline | 6.39 log10 IU/mL | Standard Deviation 0.455 |
| PF-00868554 450 mg (Cohort A) | Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 4 (Cohort B): Modified Analysis Set | Change at Day 4 | -2.15 log10 IU/mL | Standard Deviation 0.252 |
Primary
Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Nadir: Full Analysis Set
Plasma HCV RNA levels were quantified using the Abbott RealTime HCV assay (LLOQ = 12 IU/mL). Change from baseline in plasma Log10 HCV RNA at nadir signified the maximum change observed during the study.
Time frame: Baseline, Nadir (lowest HCV RNA level), assessed up to Day 11 for Cohort A and Day 4 for Cohort B
Population: FAS included all randomized participants who took at least 1 dose of study medication and had both baseline and at least 1 valid post-baseline endpoint measurements for HCV viral load.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PF-00868554 450 mg (Cohort A) | Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Nadir: Full Analysis Set | -2.2 log10 IU/mL | Standard Deviation 0.23 |
| PF-00868554 700 mg (Cohort B) | Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Nadir: Full Analysis Set | -2.3 log10 IU/mL | Standard Deviation 0.34 |
Primary
Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Nadir: Modified Analysis Set
Plasma HCV RNA levels were quantified using the Abbott RealTime HCV assay (LLOQ = 12 IU/mL). Change from baseline in plasma Log10 HCV RNA at nadir signified the maximum change observed during the study.
Time frame: Baseline, Nadir (lowest HCV RNA level), assessed up to Day 11 for Cohort A and Day 4 for Cohort B
Population: MAS: a subset of FAS which included all participants who had received complete dosage in the corresponding treatment regimen.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PF-00868554 450 mg (Cohort A) | Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Nadir: Modified Analysis Set | -2.2 log10 IU/mL | Standard Deviation 0.23 |
| PF-00868554 700 mg (Cohort B) | Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Nadir: Modified Analysis Set | -2.3 log10 IU/mL | Standard Deviation 0.34 |
Secondary
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau)
Area under the concentration curve from time 0 to end of dosing interval (AUCtau), where dosing interval was 12 hours. AUCtau was evaluated at first dose on Day 1 for Cohort A and B, and at last dose for Cohort A (Day 10) and Cohort B (Day 3).
Time frame: Predose, 0.5, 1, 2, 6, 8, 12 hours (hrs) postdose on Day 1 for Cohort A and B, pre-evening dose, 0.5, 1, 2, 4, 6, 8, 12 hrs post-evening dose on Day 3 for Cohort B, predose, 0.5, 1, 2, 4, 8, 12 hrs postdose on Day 10 for Cohort A
Population: Per Protocol (PP) analysis set included all participants who took PF-00866554 and had sufficient plasma concentration data to facilitate calculation of the pharmacokinetic (PK) parameters. Here 'n' signifies those participants who were evaluable for this measure at specified time points for each arm, respectively.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| PF-00868554 450 mg (Cohort A) | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) | Day 1 (n=10, 10) | 140275.9 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 38990.36 |
| PF-00868554 450 mg (Cohort A) | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) | Day 3 for Cohort B (n=0, 10) | NA nanogram*hour/milliliter (ng*hr/mL) | — |
| PF-00868554 450 mg (Cohort A) | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) | Day 10 for Cohort A (n=10, 0) | 139239.7 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 94286.82 |
| PF-00868554 700 mg (Cohort B) | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) | Day 1 (n=10, 10) | 198506.9 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 79422.27 |
| PF-00868554 700 mg (Cohort B) | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) | Day 3 for Cohort B (n=0, 10) | 291172.4 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 184959.54 |
| PF-00868554 700 mg (Cohort B) | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) | Day 10 for Cohort A (n=10, 0) | NA nanogram*hour/milliliter (ng*hr/mL) | — |
Secondary
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)]
AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞). AUC (0 - ∞) was evaluated at last dose for Cohort A (Day 10) and Cohort B (Day 3).
Time frame: Pre-morning dose, pre-evening dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hrs post-evening dose on Day 3 for Cohort B, predose,0.5, 1, 2, 4, 8, 12, 24, 48 hrs postdose on Day 10 for Cohort A
Population: PP analysis set. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. Results are reported for Cohort B at Day 3. Due to differences in sampling schedules between Cohort A and B, AUC (0 - ∞) data was not considered meaningful and hence were not analyzed on Day 10 for Cohort A.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-00868554 700 mg (Cohort B) | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] | 346170.1 ng*hr/mL | Standard Deviation 250370.33 |
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
Area under the serum concentration time-curve from zero to the last measured concentration (AUClast). AUClast was evaluated at first dose on Day 1 for Cohort A and B, and at last dose for Cohort A (Day 10) and Cohort B (Day 3).
Time frame: Predose, 0.5, 1, 2, 6, 8, 12, 14 hrs postdose on Day 1 for Cohort A, B, pre-morning dose, pre-evening dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hrs post-evening dose on Day 3 for Cohort B, predose,0.5, 1, 2, 4, 8, 12, 24, 48 hrs postdose on Day 10 for Cohort A
Population: PP analysis set. 'N' (number of participants analyzed) = participants evaluable for this measure. 'n' = participants evaluable for this measure at specified time points for each arm, respectively. Given the sampling schedule on Day 1 and Day 10 for 450 mg dose in Cohort A, AUClast data was not considered meaningful and hence were not analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| PF-00868554 700 mg (Cohort B) | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | Day 1 (n=0, 10) | 239697.9 ng*hr/mL | Standard Deviation 93463.98 |
| PF-00868554 700 mg (Cohort B) | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | Day 3 for Cohort B (n=0, 10) | 344075.5 ng*hr/mL | Standard Deviation 248444.34 |
Secondary
Maximum Observed Plasma Concentration (Cmax)
Cmax was evaluated at first dose on Day 1 for Cohort A and B, and at last dose for Cohort A (Day 10) and Cohort B (Day 3).
Time frame: Predose, 0.5, 1, 2, 6, 8, 12, 14 hrs postdose on Day 1 for Cohort A, B, pre-morning dose, pre-evening dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hrs post-evening dose on Day 3 for Cohort B, predose,0.5, 1, 2, 4, 8, 12, 24, 48 hrs postdose on Day 10 for Cohort A
Population: PP analysis set included all participants who took PF-00866554 and had sufficient plasma concentration data to facilitate calculation of the PK parameters. Here 'n' signifies those participants who were evaluable for this measure at specified time points for each arm, respectively.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| PF-00868554 450 mg (Cohort A) | Maximum Observed Plasma Concentration (Cmax) | Day 1 (n=10, 10) | 44688.1 ng/mL | Standard Deviation 13542.3 |
| PF-00868554 450 mg (Cohort A) | Maximum Observed Plasma Concentration (Cmax) | Day 3 for Cohort B (n=0, 10) | NA ng/mL | — |
| PF-00868554 450 mg (Cohort A) | Maximum Observed Plasma Concentration (Cmax) | Day 10 for Cohort A (n=10, 0) | 42859.7 ng/mL | Standard Deviation 16697.78 |
| PF-00868554 700 mg (Cohort B) | Maximum Observed Plasma Concentration (Cmax) | Day 1 (n=10, 10) | 38734.5 ng/mL | Standard Deviation 14464.27 |
| PF-00868554 700 mg (Cohort B) | Maximum Observed Plasma Concentration (Cmax) | Day 3 for Cohort B (n=0, 10) | 50274.1 ng/mL | Standard Deviation 22297.74 |
| PF-00868554 700 mg (Cohort B) | Maximum Observed Plasma Concentration (Cmax) | Day 10 for Cohort A (n=10, 0) | NA ng/mL | — |
Secondary
Plasma Concentration at The End of Dosing Interval (Ctau)
Ctau was evaluated at first dose on Day 1 for Cohort A and B, and at last dose for Cohort A (Day 10) and Cohort B (Day 3).
Time frame: Predose, 0.5, 1, 2, 6, 8, 12 hours (hrs) postdose on Day 1 for Cohort A and B, pre-evening dose, 0.5, 1, 2, 4, 6, 8, 12 hrs post-evening dose on Day 3 for Cohort B, predose, 0.5, 1, 2, 4, 8, 12 hrs postdose on Day 10 for Cohort A
Population: PP analysis set. Here 'n' signifies those participants who were evaluable for this measure at specified time points for each arm, respectively. The Ctau on Day 1 was not necessary for interpretation of the PK data and hence was not analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| PF-00868554 450 mg (Cohort A) | Plasma Concentration at The End of Dosing Interval (Ctau) | Day 10 for Cohort A (n=10, 0) | 1435.2 ng/mL | Standard Deviation 3065.84 |
| PF-00868554 450 mg (Cohort A) | Plasma Concentration at The End of Dosing Interval (Ctau) | Day 3 for Cohort B (n=0, 10) | NA ng/mL | — |
| PF-00868554 700 mg (Cohort B) | Plasma Concentration at The End of Dosing Interval (Ctau) | Day 3 for Cohort B (n=0, 10) | 6572.0 ng/mL | Standard Deviation 9550.56 |
| PF-00868554 700 mg (Cohort B) | Plasma Concentration at The End of Dosing Interval (Ctau) | Day 10 for Cohort A (n=10, 0) | NA ng/mL | — |
Secondary
Plasma Decay Half-Life (t1/2)
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. Half-life was evaluated at last dose for Cohort A (Day 10) and Cohort B (Day 3).
Time frame: Pre-morning dose, pre-evening dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hrs post-evening dose on Day 3 for Cohort B, predose,0.5, 1, 2, 4, 8, 12, 24, 48 hrs postdose on Day 10 for Cohort A
Population: PP analysis set. 'N' (number of participants analyzed) = participants evaluable for this measure. Results are reported for Cohort B at Day 3. Due to limited sampling, time interval over which plasma concentrations were measured after final dose was too short relative to projected t1/2. Therefore, t1/2 estimates were not calculated on Day 10.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PF-00868554 700 mg (Cohort B) | Plasma Decay Half-Life (t1/2) | 7.468 hours | Standard Deviation 1.3235 |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Tmax was evaluated at first dose on Day 1 for Cohort A and B, and at last dose for Cohort A (Day 10) and Cohort B (Day 3).
Time frame: Predose, 0.5, 1, 2, 6, 8, 12, 14 hrs postdose on Day 1 for Cohort A, B, pre-morning dose, pre-evening dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hrs post-evening dose on Day 3 for Cohort B, predose,0.5, 1, 2, 4, 8, 12, 24, 48 hrs postdose on Day 10 for Cohort A
Population: PP analysis set included all participants who took PF-00866554 and had sufficient plasma concentration data to facilitate calculation of the PK parameters. Here 'n' signifies those participants who were evaluable for this measure at specified time points for each arm, respectively.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| PF-00868554 450 mg (Cohort A) | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 1 (n=10, 10) | 0.750 hours |
| PF-00868554 450 mg (Cohort A) | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 3 for Cohort B (n=0, 10) | NA hours |
| PF-00868554 450 mg (Cohort A) | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 10 for Cohort A (n=10, 0) | 1.000 hours |
| PF-00868554 700 mg (Cohort B) | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 1 (n=10, 10) | 2.000 hours |
| PF-00868554 700 mg (Cohort B) | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 3 for Cohort B (n=0, 10) | 2.000 hours |
| PF-00868554 700 mg (Cohort B) | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 10 for Cohort A (n=10, 0) | NA hours |