Trial Outcomes & Findings for A Study To Estimate The Effect of PF-06650833 On The Pharmacokinetics (PK) of Oral Contraceptive (OC) (NCT NCT05064332)

Results Overview

AUClast was defined as area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration. AUClast for EE was determined using linear/Log trapezoidal method.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

10 participants

Primary outcome timeframe

Predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36 and 48 hours post OC dose in Periods 1 and 2

Results posted on

2023-10-02

Participant Flow

Participants were screened 28 days prior to the first dose of study intervention in Period 1 and reported to the clinical research unit the day prior to Day 1 dosing in Period 1.

The study consisted of 2 periods in a single fixed sequence. Period 1 was immediately followed by Period 2 with no washout. A total of 10 participants were enrolled in the study.

Participant milestones

Participant milestones
Measure	Oral Contraceptive (OC) Then PF-06650833+ OC Participants received a single oral dose of OC, containing ethinyl estradiol (EE) 30 microgram (mcg) and levonorgestrel (LN) 150 mcg on Day 1 Period 1. After completion of Period 1, participants orally received PF-06650833 400 milligram (mg) once daily (QD) on Days 1-11 of Period 2 and a single oral dose of OC, containing EE 30 mcg and LN 150 mcg on Day 10 Period 2.
Period 1 STARTED	10
Period 1 COMPLETED	10
Period 1 NOT COMPLETED	0
Period 2 STARTED	10
Period 2 COMPLETED	10
Period 2 NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study To Estimate The Effect of PF-06650833 On The Pharmacokinetics (PK) of Oral Contraceptive (OC)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	OC Then PF-06650833+ OC n=10 Participants Participants received a single oral dose of OC, containing EE 30 mcg and LN 150 mcg on Day 1 Period 1. After completion of Period 1, participants orally received PF-06650833 400 mg QD on Days 1-11 of Period 2 and a single oral dose of OC, containing of EE 30 mcg and LN 150 mcg on Day 10 Period 2.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	10 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	10 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36 and 48 hours post OC dose in Periods 1 and 2

Population: The PK parameter analysis population was defined as all participants that received at least 1 dose of study intervention and had at least 1 of the PK parameters of primary interest reported in at least 1 period.

AUClast was defined as area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration. AUClast for EE was determined using linear/Log trapezoidal method.

Outcome measures

Outcome measures
Measure	Period 1: Oral Contraceptive n=10 Participants Participants received a single oral dose of OC, containing EE 30 mcg and LN 150 mcg on Day 1 Period 1.	Period 2: PF-06650833 + Oral Contraceptive n=10 Participants Participants orally received PF-06650833 400 mg QD on Days 1-11 of Period 2 and a single oral dose of OC, containing of EE 30 mcg and LN 150 mcg on Day 10 Period 2.	Period 2: PF-06650833 + Oral Contraceptive Participants received a single oral dose of OC, containing of EE 30 mcg and LN 150 mcg on Day 10 Period 2 and a single oral dose of PF-06650833 400 mg on Day 11 Period 2.
Area Under the Plasma Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for Ethinyl Estradiol	812.3 picogramhour per milliliter (pghr/mL) Geometric Coefficient of Variation 25	823.9 picogramhour per milliliter (pghr/mL) Geometric Coefficient of Variation 26	—

PRIMARY outcome

Timeframe: Predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36 and 48 hours post OC dose in Periods 1 and 2

Population: The PK parameter analysis population was defined as all participants that received at least 1 dose of study intervention and had at least 1 of the PK parameters of primary interest reported in at least 1 period.

AUClast was defined as area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration. AUClast for LN was determined using linear/Log trapezoidal method.

Outcome measures

Outcome measures
Measure	Period 1: Oral Contraceptive n=10 Participants Participants received a single oral dose of OC, containing EE 30 mcg and LN 150 mcg on Day 1 Period 1.	Period 2: PF-06650833 + Oral Contraceptive n=10 Participants Participants orally received PF-06650833 400 mg QD on Days 1-11 of Period 2 and a single oral dose of OC, containing of EE 30 mcg and LN 150 mcg on Day 10 Period 2.	Period 2: PF-06650833 + Oral Contraceptive Participants received a single oral dose of OC, containing of EE 30 mcg and LN 150 mcg on Day 10 Period 2 and a single oral dose of PF-06650833 400 mg on Day 11 Period 2.
Area Under the Plasma Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration for Levonorgestrel	31510 pg*hr/mL Geometric Coefficient of Variation 39	34190 pg*hr/mL Geometric Coefficient of Variation 41	—

PRIMARY outcome

Timeframe: Predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36 and 48 hours post OC dose in Periods 1 and 2

Population: The PK parameter analysis population was defined as all participants that received at least 1 dose of study intervention and had at least 1 of the PK parameters of primary interest reported in at least 1 period.

Cmax was defined as maximum plasma concentration. Cmax for EE was observed directly from data.

Outcome measures

Outcome measures
Measure	Period 1: Oral Contraceptive n=10 Participants Participants received a single oral dose of OC, containing EE 30 mcg and LN 150 mcg on Day 1 Period 1.	Period 2: PF-06650833 + Oral Contraceptive n=10 Participants Participants orally received PF-06650833 400 mg QD on Days 1-11 of Period 2 and a single oral dose of OC, containing of EE 30 mcg and LN 150 mcg on Day 10 Period 2.	Period 2: PF-06650833 + Oral Contraceptive Participants received a single oral dose of OC, containing of EE 30 mcg and LN 150 mcg on Day 10 Period 2 and a single oral dose of PF-06650833 400 mg on Day 11 Period 2.
Maximum Plasma Concentration (Cmax) for Ethinyl Estradiol	84.00 picogram per milliliter (pg/mL) Geometric Coefficient of Variation 38	79.86 picogram per milliliter (pg/mL) Geometric Coefficient of Variation 26	—

PRIMARY outcome

Timeframe: Predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36 and 48 hours post OC dose in Periods 1 and 2

Population: The PK parameter analysis population was defined as all participants that received at least 1 dose of study intervention and had at least 1 of the PK parameters of primary interest reported in at least 1 period.

Cmas was defined as maximum plasma concentration. Cmax for LN was observed directly from data.

Outcome measures

Outcome measures
Measure	Period 1: Oral Contraceptive n=10 Participants Participants received a single oral dose of OC, containing EE 30 mcg and LN 150 mcg on Day 1 Period 1.	Period 2: PF-06650833 + Oral Contraceptive n=10 Participants Participants orally received PF-06650833 400 mg QD on Days 1-11 of Period 2 and a single oral dose of OC, containing of EE 30 mcg and LN 150 mcg on Day 10 Period 2.	Period 2: PF-06650833 + Oral Contraceptive Participants received a single oral dose of OC, containing of EE 30 mcg and LN 150 mcg on Day 10 Period 2 and a single oral dose of PF-06650833 400 mg on Day 11 Period 2.
Maximum Plasma Concentration for Levonorgestrel	3468 pg/mL Geometric Coefficient of Variation 56	4092 pg/mL Geometric Coefficient of Variation 53	—

SECONDARY outcome

Timeframe: From the first dose up to 35 days after the last dose of study intervention

Population: The safety analysis set was defined as all participants enrolled to study intervention and who took at least 1 dose of study intervention.

An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An serious adverse event (SAE) was defined as an AE: 1. resulting in death, 2. was life-threatening, 3. required inpatient hospitalization or prolongation of existing hospitalization, 4. resulted in persistent disability, 5. was a congenital anomaly/birth defect, or considered to be an important medical event. Treatment-related AE was any untoward medical occurrence attributed to study intervention in a participant who received study intervention. Treatment-emergent are events between first dose of study intervention and up to 35 days after last dose that were absent before treatment or that worsened relative to pretreatment state.

Outcome measures

Outcome measures
Measure	Period 1: Oral Contraceptive n=10 Participants Participants received a single oral dose of OC, containing EE 30 mcg and LN 150 mcg on Day 1 Period 1.	Period 2: PF-06650833 + Oral Contraceptive n=10 Participants Participants orally received PF-06650833 400 mg QD on Days 1-11 of Period 2 and a single oral dose of OC, containing of EE 30 mcg and LN 150 mcg on Day 10 Period 2.	Period 2: PF-06650833 + Oral Contraceptive n=10 Participants Participants received a single oral dose of OC, containing of EE 30 mcg and LN 150 mcg on Day 10 Period 2 and a single oral dose of PF-06650833 400 mg on Day 11 Period 2.
Number of Participants With Treatment Emergent Treatment-Related Adverse Events Treatment-related AEs	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment Emergent Treatment-Related Adverse Events Treatment-related SAEs	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From the first dose up to 35 days after the last dose of study intervention

Population: The safety analysis set was defined as all participants enrolled to study intervention and who took at least 1 dose of study intervention.

An AE was any untoward medical occurrence attributed to study intervention in a participant who received study intervention. AEs are classified according to the severity in 3 categories. a) mild - AEs does not interfere with participant's usual function; b) moderate - AEs interferes to some extent with participant's usual function; c) severe - AEs interferes significantly with participant's usual function. Only those categories in which at least 1 participant had data were reported.

Outcome measures

Outcome measures
Measure	Period 1: Oral Contraceptive n=10 Participants Participants received a single oral dose of OC, containing EE 30 mcg and LN 150 mcg on Day 1 Period 1.	Period 2: PF-06650833 + Oral Contraceptive n=10 Participants Participants orally received PF-06650833 400 mg QD on Days 1-11 of Period 2 and a single oral dose of OC, containing of EE 30 mcg and LN 150 mcg on Day 10 Period 2.	Period 2: PF-06650833 + Oral Contraceptive n=10 Participants Participants received a single oral dose of OC, containing of EE 30 mcg and LN 150 mcg on Day 10 Period 2 and a single oral dose of PF-06650833 400 mg on Day 11 Period 2.
Number of Participants With Treatment Emergent Adverse Events by Severity Nausea (mild)	0 Participants	1 Participants	0 Participants
Number of Participants With Treatment Emergent Adverse Events by Severity Toothache (mild)	0 Participants	0 Participants	1 Participants
Number of Participants With Treatment Emergent Adverse Events by Severity Headache (mild)	0 Participants	1 Participants	0 Participants
Number of Participants With Treatment Emergent Adverse Events by Severity Pruritus (mild)	0 Participants	2 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 1 for Period 1 and Day 1, Day 10, Day 12 for Period 2

Population: The safety analysis set was defined as all participants enrolled to study intervention and who took at least 1 dose of study intervention.

Systolic blood pressure (BP), diastolic BP and supine pulse rate measurements meeting the criteria of potential clinical concern were summarized by treatment using categories as defined: Systolic BP min. \<90 mmHg; Systolic BP max. decrease ≥30 or max. increase ≥30; Diastolic BP min. \<50 mmHg; Diastolic BP max. decrease ≥20 or max. increase ≥20; Supine pulse rate min. \<40 bpm or max. \>120 bpm.

Outcome measures

Outcome measures
Measure	Period 1: Oral Contraceptive n=10 Participants Participants received a single oral dose of OC, containing EE 30 mcg and LN 150 mcg on Day 1 Period 1.	Period 2: PF-06650833 + Oral Contraceptive n=10 Participants Participants orally received PF-06650833 400 mg QD on Days 1-11 of Period 2 and a single oral dose of OC, containing of EE 30 mcg and LN 150 mcg on Day 10 Period 2.	Period 2: PF-06650833 + Oral Contraceptive Participants received a single oral dose of OC, containing of EE 30 mcg and LN 150 mcg on Day 10 Period 2 and a single oral dose of PF-06650833 400 mg on Day 11 Period 2.
Number of Participants With Categorical Vital Signs Data of Potential Clinical Concern	0 Participants	0 Participants	—

SECONDARY outcome

Timeframe: Day 10, Day 12 for Period 2

Population: The safety analysis set was defined as all participants enrolled to study intervention and who took at least 1 dose of study intervention.

Hematology (hemoglobin, hematocrit, erythrocytes \[Ery.\], Ery.mean corpuscular volume, Ery.mean corpuscular hemoglobin, platelets, leukocytes, lymphocytes, neutrophils, basophils, eosinophils, monocytes); clinical chemistry (bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, protein, albumin, urea nitrogen, creatinine, urate, sodium, potassium, chloride, calcium, bicarbonate, glucose, creatine kinase); and urinalysis (pH, glucose, ketones, protein, hemoglobin, urobilinogen, bilirubin, nitrite, leukocyte esterase, Ery., leukocytes, epithelial cells, casts and bacteria) tests were assessed. Only those categories, in which at least 1 participant had data were reported.

Outcome measures

Outcome measures
Measure	Period 1: Oral Contraceptive n=10 Participants Participants received a single oral dose of OC, containing EE 30 mcg and LN 150 mcg on Day 1 Period 1.	Period 2: PF-06650833 + Oral Contraceptive Participants orally received PF-06650833 400 mg QD on Days 1-11 of Period 2 and a single oral dose of OC, containing of EE 30 mcg and LN 150 mcg on Day 10 Period 2.	Period 2: PF-06650833 + Oral Contraceptive Participants received a single oral dose of OC, containing of EE 30 mcg and LN 150 mcg on Day 10 Period 2 and a single oral dose of PF-06650833 400 mg on Day 11 Period 2.
Number of Participants With Laboratory Abnormalities of Potential Clinical Concern Urine Hemoglobin ≥1	5 Participants	—	—
Number of Participants With Laboratory Abnormalities of Potential Clinical Concern Leukocyte Esterase ≥1	2 Participants	—	—

Adverse Events

Period 1: Oral Contraceptive

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Period 2: PF-06650833

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Period 2: PF-06650833 + Oral Contraceptive

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	Period 1: Oral Contraceptive n=10 participants at risk Participants received a single oral dose of OC, containing EE 30 mcg and LN 150 mcg on Day 1 Period 1.	Period 2: PF-06650833 n=10 participants at risk Participants orally received PF-06650833 400 mg QD on Days 1-10 of Period 2.	Period 2: PF-06650833 + Oral Contraceptive n=10 participants at risk Participants received a single oral dose of OC, containing of EE 30 mcg and LN 150 mcg on Day 10 Period 2 and a single oral dose of PF-06650833 400 mg on Day 11 Period 2.
Gastrointestinal disorders Nausea	0.00% 0/10 • From the first dose up to 35 days after the last dose of study intervention. MedDRA 24.1 coding dictionary was applied for all AE tables. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	10.0% 1/10 • From the first dose up to 35 days after the last dose of study intervention. MedDRA 24.1 coding dictionary was applied for all AE tables. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/10 • From the first dose up to 35 days after the last dose of study intervention. MedDRA 24.1 coding dictionary was applied for all AE tables. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Gastrointestinal disorders Toothache	0.00% 0/10 • From the first dose up to 35 days after the last dose of study intervention. MedDRA 24.1 coding dictionary was applied for all AE tables. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/10 • From the first dose up to 35 days after the last dose of study intervention. MedDRA 24.1 coding dictionary was applied for all AE tables. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	10.0% 1/10 • From the first dose up to 35 days after the last dose of study intervention. MedDRA 24.1 coding dictionary was applied for all AE tables. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Nervous system disorders Headache	0.00% 0/10 • From the first dose up to 35 days after the last dose of study intervention. MedDRA 24.1 coding dictionary was applied for all AE tables. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	10.0% 1/10 • From the first dose up to 35 days after the last dose of study intervention. MedDRA 24.1 coding dictionary was applied for all AE tables. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/10 • From the first dose up to 35 days after the last dose of study intervention. MedDRA 24.1 coding dictionary was applied for all AE tables. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/10 • From the first dose up to 35 days after the last dose of study intervention. MedDRA 24.1 coding dictionary was applied for all AE tables. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	20.0% 2/10 • From the first dose up to 35 days after the last dose of study intervention. MedDRA 24.1 coding dictionary was applied for all AE tables. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/10 • From the first dose up to 35 days after the last dose of study intervention. MedDRA 24.1 coding dictionary was applied for all AE tables. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.

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 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