Healthy Postmenopausal Females
Conditions
Brief summary
For the contraceptive application a film-coated tablet has been developed which combines nomegestrol acetate (NOMAC) with estradiol (E2). This was an open-label, randomized, single-dose, four-way, replicate, cross-over study design conducted in 2 parallel parts at two sites, one site per study part. The primary objective of Part 1 was to assess the bioequivalence of NOMAC and E2 of the drug product manufactured using the commercial process (commercial batch) versus the Phase 3 drug product (Batch A). The primary objective of Part 2 was to assess bioequivalence of NOMAC and E2 of the drug product manufactured using the commercial process (commercial batch) versus the Phase 3 drug product (Batch B).
Interventions
DRUGCommercial NOMAC-E2
1 x 2.5 mg NOMAC/1.5 mg E2 fixed dose combination commercial tablet orally in the morning on Day 1 for all periods
DRUGPhase 3 NOMAC-E2 Batch A
1 x 2.5 mg NOMAC/1.5 mg E2 fixed dose combination tablet from the Phase 3 clinical trial program (Batch A) orally in the morning on Day 1 for all periods
DRUGPhase 3 NOMAC-E2 Batch B
1 x 2.5 mg NOMAC/1.5 mg E2 fixed dose combination tablet from the Phase 3 clinical trial program (Batch B) orally in the morning on Day 1 for all periods
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
45 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: * Healthy postmenopausal females between the ages of 45 and 70 years, inclusive, having a Body Mass Index (BMI) between 18 and 32, inclusive; * Free of any clinically significant disease that would interfere with the study evaluations. Key
Exclusion criteria
* Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug; * History of any infectious disease that affected the subject's ability to participate in the trial; * History of alcohol or drug abuse in the past 2 years; * Previously received NOMAC-E2; * Current participation in another clinical study or had participated in a clinical study (eg, laboratory or clinical evaluation) within 30 days of baseline; * Smoked more than 10 cigarettes or equivalent tobacco use per day; * History of malignancy; * Contraindications for the use of contraceptive steroids; * Recent history of medication use of certain medications specified in the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration of NOMAC (Cmax of NOMAC) | 0 hours to time of maximum observed plasma concentration of NOMAC (tmax of NOMAC) (blood samples were collected for NOMAC evaluation up to 144 hours postdose) | Bioequivalence for NOMAC and E2 were tested on the primary PK parameters: Cmax, AUC(infinity), and AUClast for NOMAC; and baseline adjusted AUC72 and Cmax for E2. Blood samples for pharmacokinetic (PK) evaluation of NOMAC were collected at predose (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 144 hours postdose Day 1. |
| Baseline Corrected Maximum Observed Serum Concentration of E2 (Cmax of E2) | 0 hours to time of maximum observed serum concentration of E2 (tmax of E2) (blood samples were collected for E2 evaluation up to 96 hours postdose) | Bioequivalence for NOMAC and E2 were tested on the primary PK parameters: Cmax, AUC(infinity), and AUClast for NOMAC; and baseline adjusted AUC72 and Cmax for E2. Blood samples for PK evaluation of E2 were collected predose (-1, -0.5, and 0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose Day 1; multiple predose samples were needed to correct for endogenous levels. |
| Area Under the Concentration-time Curve From Time 0 to the Time of the Last Measurable Sample (AUC Last) and Area Under the Concentration-time Curve From Time 0 to Infinity (AUC Infinity) for NOMAC | 0 hours to time of the last measurable sample (blood samples were collected for NOMAC evaluation up to 144 hours postdose) | Bioequivalence for NOMAC and E2 were tested on the primary PK parameters: Cmax, AUC(infinity), and AUClast for NOMAC; and baseline adjusted AUC72 and Cmax for E2. AUClast is the AUC from time 0 to the time of the final quantifiable sample. AUC infinity is the AUC from time 0 to infinity. Blood samples for PK evaluation of NOMAC were collected at predose (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 144 hours postdose Day 1. |
| Baseline Corrected Area Under the Concentration-time Curve From Time 0 to 72 Hours (AUC72) for E2 | 0 hours to 72 hours | Bioequivalence for NOMAC and E2 were tested on the primary PK parameters: Cmax, AUC(infinity), and AUClast for NOMAC; and baseline adjusted AUC72 and Cmax for E2. AUC72 is the AUC from time 0 to 72 hours. Blood samples for PK evaluation of E2 were collected predose (-1, -0.5, and 0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose Day 1; multiple predose samples were needed to correct for endogenous levels. |
Secondary
| Measure | Time frame |
|---|---|
| Clearance (Calculated for NOMAC Only) | blood samples were collected for NOMAC evaluation up to 144 hours postdose |
| Tmax of NOMAC | 0 hours to tmax of NOMAC (blood samples were collected for NOMAC evaluation up to 144 hours postdose) |
| Volume of Distribution (Calculated for NOMAC Only) | blood samples were collected for NOMAC evaluation up to 144 hours postdose |
| Tmax of E2 | 0 hours to tmax of E2 (blood samples were collected for E2 evaluation up to 96 hours postdose) |
| Terminal Phase Half Life (t1/2) of NOMAC | 0 hours to t1/2 (blood samples were collected for NOMAC evaluation up to 144 hours postdose) |
| t1/2 of E2 | 0 hours to t1/2 (blood samples were collected for E2 evaluation up to 96 hours postdose) |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part 1 - Sequence 1 Participants received a single oral dose of the NOMAC-E2 fixed-dose combination commercial tablet (2.5 mg NOMAC/1.5 mg E2) on the first day of Period 1 and Period 3; Participants received a single oral dose of the NOMAC-E2 fixed-dose combination tablet (2.5 mg NOMAC/1.5 mg E2) from the Phase 3 clinical trial program (Batch A) on the first day of Period 2 and Period 4. Participants in Part 1 were from Site 1. | 41 |
| Part 1 - Sequence 2 Participants received a single oral dose of the NOMAC-E2 fixed-dose combination tablet (2.5 mg NOMAC/1.5 mg E2) from the Phase 3 clinical trial program (Batch A) on the first day of Period 1 and Period 3; Participants received a single oral dose of the NOMAC-E2 fixed-dose combination commercial tablet (2.5 mg NOMAC/1.5 mg E2) on the first day of Period 2 and Period 4. Participants in Part 1 were from Site 1. | 41 |
| Part 2 - Sequence 1 Participants received a single oral dose of the NOMAC-E2 fixed-dose combination commercial tablet (2.5 mg NOMAC/1.5 mg E2) on the first day of Period 1 and Period 3; Participants received a single oral dose of the NOMAC-E2 fixed-dose combination tablet (2.5 mg NOMAC/1.5 mg E2) from the Phase 3 clinical trial program (Batch B) on the first day of Period 2 and Period 4. Participants in Part 2 were from Site 2. | 37 |
| Part 2 - Sequence 2 Participants received a single oral dose of the NOMAC-E2 fixed-dose combination tablet (2.5 mg NOMAC/1.5 mg E2) from the Phase 3 clinical trial program (Batch B) on the first day of Period 1 and Period 3; Participants received a single oral dose of the NOMAC-E2 fixed-dose combination commercial tablet (2.5 mg NOMAC/1.5 mg E2) on the first day of Period 2 and Period 4. Participants in Part 2 were from Site 2. | 37 |
| Total | 156 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Administrative | 3 | 5 | 0 | 0 |
| Overall Study | Adverse Event | 0 | 1 | 3 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 2 |
| Overall Study | Noncompliance with protocol | 1 | 0 | 1 | 0 |
| Overall Study | Subject withdrew consent | 2 | 2 | 1 | 0 |
Baseline characteristics
| Characteristic | Part 1 - Sequence 1 | Part 1 - Sequence 2 | Part 2 - Sequence 1 | Part 2 - Sequence 2 | Total |
|---|---|---|---|---|---|
| Age, Continuous | 55.3 years | 55.5 years | 55.9 years | 56.5 years | 55.78 years |
| Sex: Female, Male Female | 41 Participants | 41 Participants | 37 Participants | 37 Participants | 156 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 44 / 80 | 35 / 77 | 36 / 72 | 35 / 72 |
| serious Total, serious adverse events | 0 / 80 | 0 / 77 | 0 / 72 | 0 / 72 |
Outcome results
Primary
Area Under the Concentration-time Curve From Time 0 to the Time of the Last Measurable Sample (AUC Last) and Area Under the Concentration-time Curve From Time 0 to Infinity (AUC Infinity) for NOMAC
Bioequivalence for NOMAC and E2 were tested on the primary PK parameters: Cmax, AUC(infinity), and AUClast for NOMAC; and baseline adjusted AUC72 and Cmax for E2. AUClast is the AUC from time 0 to the time of the final quantifiable sample. AUC infinity is the AUC from time 0 to infinity. Blood samples for PK evaluation of NOMAC were collected at predose (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 144 hours postdose Day 1.
Time frame: 0 hours to time of the last measurable sample (blood samples were collected for NOMAC evaluation up to 144 hours postdose)
Population: The # of plasma profiles analyzed is based on the # of single-dose administration periods actually completed (some participants discontinued without completing all 4 dosing periods).~Part 1 analyses also excluded certain data from participants who were misdosed, and Part 2 analyses excluded participants who did not receive drug.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Commercial NOMAC-E2, Part 1 | Area Under the Concentration-time Curve From Time 0 to the Time of the Last Measurable Sample (AUC Last) and Area Under the Concentration-time Curve From Time 0 to Infinity (AUC Infinity) for NOMAC | AUC last | 87.3 ng*h/mL |
| Commercial NOMAC-E2, Part 1 | Area Under the Concentration-time Curve From Time 0 to the Time of the Last Measurable Sample (AUC Last) and Area Under the Concentration-time Curve From Time 0 to Infinity (AUC Infinity) for NOMAC | AUC infinity | 102 ng*h/mL |
| Phase 3 NOMAC-E2, Part 1 | Area Under the Concentration-time Curve From Time 0 to the Time of the Last Measurable Sample (AUC Last) and Area Under the Concentration-time Curve From Time 0 to Infinity (AUC Infinity) for NOMAC | AUC infinity | 93.3 ng*h/mL |
| Phase 3 NOMAC-E2, Part 1 | Area Under the Concentration-time Curve From Time 0 to the Time of the Last Measurable Sample (AUC Last) and Area Under the Concentration-time Curve From Time 0 to Infinity (AUC Infinity) for NOMAC | AUC last | 78.1 ng*h/mL |
| Commercial NOMAC-E2, Part 2 | Area Under the Concentration-time Curve From Time 0 to the Time of the Last Measurable Sample (AUC Last) and Area Under the Concentration-time Curve From Time 0 to Infinity (AUC Infinity) for NOMAC | AUC last | 109 ng*h/mL |
| Commercial NOMAC-E2, Part 2 | Area Under the Concentration-time Curve From Time 0 to the Time of the Last Measurable Sample (AUC Last) and Area Under the Concentration-time Curve From Time 0 to Infinity (AUC Infinity) for NOMAC | AUC infinity | 134 ng*h/mL |
| Phase 3 NOMAC-E2, Part 2 | Area Under the Concentration-time Curve From Time 0 to the Time of the Last Measurable Sample (AUC Last) and Area Under the Concentration-time Curve From Time 0 to Infinity (AUC Infinity) for NOMAC | AUC last | 106 ng*h/mL |
| Phase 3 NOMAC-E2, Part 2 | Area Under the Concentration-time Curve From Time 0 to the Time of the Last Measurable Sample (AUC Last) and Area Under the Concentration-time Curve From Time 0 to Infinity (AUC Infinity) for NOMAC | AUC infinity | 131 ng*h/mL |
Comparison: Analysis for AUClast90% CI: [106.4, 113.7]
Comparison: Analysis for AUC last90% CI: [100.9, 105.7]
Comparison: Analysis for AUC infinity90% CI: [104.7, 111.6]
Comparison: Analysis for AUC infinity90% CI: [100.5, 105.8]
Primary
Baseline Corrected Area Under the Concentration-time Curve From Time 0 to 72 Hours (AUC72) for E2
Bioequivalence for NOMAC and E2 were tested on the primary PK parameters: Cmax, AUC(infinity), and AUClast for NOMAC; and baseline adjusted AUC72 and Cmax for E2. AUC72 is the AUC from time 0 to 72 hours. Blood samples for PK evaluation of E2 were collected predose (-1, -0.5, and 0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose Day 1; multiple predose samples were needed to correct for endogenous levels.
Time frame: 0 hours to 72 hours
Population: The # of plasma profiles analyzed is based on the # of single-dose administration periods actually completed (some participants discontinued without completing all 4 dosing periods).~Part 1 analyses also excluded certain data from participants who were misdosed, and Part 2 analyses excluded participants who did not receive drug.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Commercial NOMAC-E2, Part 1 | Baseline Corrected Area Under the Concentration-time Curve From Time 0 to 72 Hours (AUC72) for E2 | 1315 pg*h/mL |
| Phase 3 NOMAC-E2, Part 1 | Baseline Corrected Area Under the Concentration-time Curve From Time 0 to 72 Hours (AUC72) for E2 | 1278 pg*h/mL |
| Commercial NOMAC-E2, Part 2 | Baseline Corrected Area Under the Concentration-time Curve From Time 0 to 72 Hours (AUC72) for E2 | 1359 pg*h/mL |
| Phase 3 NOMAC-E2, Part 2 | Baseline Corrected Area Under the Concentration-time Curve From Time 0 to 72 Hours (AUC72) for E2 | 1342 pg*h/mL |
90% CI: [96.7, 106.4]
90% CI: [98.1, 104.7]
Primary
Baseline Corrected Maximum Observed Serum Concentration of E2 (Cmax of E2)
Bioequivalence for NOMAC and E2 were tested on the primary PK parameters: Cmax, AUC(infinity), and AUClast for NOMAC; and baseline adjusted AUC72 and Cmax for E2. Blood samples for PK evaluation of E2 were collected predose (-1, -0.5, and 0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose Day 1; multiple predose samples were needed to correct for endogenous levels.
Time frame: 0 hours to time of maximum observed serum concentration of E2 (tmax of E2) (blood samples were collected for E2 evaluation up to 96 hours postdose)
Population: The # of plasma profiles analyzed is based on the # of single-dose administration periods actually completed (some participants discontinued without completing all 4 dosing periods).~Part 1 analyses also excluded certain data from participants who were misdosed, and Part 2 analyses excluded participants who did not receive drug.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Commercial NOMAC-E2, Part 1 | Baseline Corrected Maximum Observed Serum Concentration of E2 (Cmax of E2) | 56.1 pg/mL |
| Phase 3 NOMAC-E2, Part 1 | Baseline Corrected Maximum Observed Serum Concentration of E2 (Cmax of E2) | 45.1 pg/mL |
| Commercial NOMAC-E2, Part 2 | Baseline Corrected Maximum Observed Serum Concentration of E2 (Cmax of E2) | 44.4 pg/mL |
| Phase 3 NOMAC-E2, Part 2 | Baseline Corrected Maximum Observed Serum Concentration of E2 (Cmax of E2) | 41.5 pg/mL |
90% CI: [99, 116.4]
90% CI: [99.2, 108.2]
Primary
Maximum Observed Plasma Concentration of NOMAC (Cmax of NOMAC)
Bioequivalence for NOMAC and E2 were tested on the primary PK parameters: Cmax, AUC(infinity), and AUClast for NOMAC; and baseline adjusted AUC72 and Cmax for E2. Blood samples for pharmacokinetic (PK) evaluation of NOMAC were collected at predose (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 144 hours postdose Day 1.
Time frame: 0 hours to time of maximum observed plasma concentration of NOMAC (tmax of NOMAC) (blood samples were collected for NOMAC evaluation up to 144 hours postdose)
Population: The # of plasma profiles analyzed is based on the # of single-dose administration periods actually completed (some participants discontinued without completing all 4 dosing periods).~Part 1 analyses also excluded certain data from participants who were misdosed, and Part 2 analyses excluded participants who did not receive drug.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Commercial NOMAC-E2, Part 1 | Maximum Observed Plasma Concentration of NOMAC (Cmax of NOMAC) | 6.22 ng/mL |
| Phase 3 NOMAC-E2, Part 1 | Maximum Observed Plasma Concentration of NOMAC (Cmax of NOMAC) | 4.51 ng/mL |
| Commercial NOMAC-E2, Part 2 | Maximum Observed Plasma Concentration of NOMAC (Cmax of NOMAC) | 8.03 ng/mL |
| Phase 3 NOMAC-E2, Part 2 | Maximum Observed Plasma Concentration of NOMAC (Cmax of NOMAC) | 7.20 ng/mL |
90% CI: [131, 144.4]
90% CI: [107.5, 116.4]
Secondary
Clearance (Calculated for NOMAC Only)
Time frame: blood samples were collected for NOMAC evaluation up to 144 hours postdose
Population: The # of plasma profiles analyzed is based on the # of single-dose administration periods actually completed (some participants discontinued without completing all 4 dosing periods).~Part 1 analyses also excluded certain data from participants who were misdosed, and Part 2 analyses excluded participants who did not receive drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Commercial NOMAC-E2, Part 1 | Clearance (Calculated for NOMAC Only) | 28.3 L/h | Standard Deviation 16.1 |
| Phase 3 NOMAC-E2, Part 1 | Clearance (Calculated for NOMAC Only) | 29.9 L/h | Standard Deviation 9.68 |
| Commercial NOMAC-E2, Part 2 | Clearance (Calculated for NOMAC Only) | 21.1 L/h | Standard Deviation 7.96 |
| Phase 3 NOMAC-E2, Part 2 | Clearance (Calculated for NOMAC Only) | 22.1 L/h | Standard Deviation 9.37 |
Secondary
t1/2 of E2
Time frame: 0 hours to t1/2 (blood samples were collected for E2 evaluation up to 96 hours postdose)
Population: The # of plasma profiles analyzed is based on the # of single-dose administration periods actually completed (some participants discontinued without completing all 4 dosing periods).~Part 1 analyses also excluded certain data from participants who were misdosed, and Part 2 analyses excluded participants who did not receive drug.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Commercial NOMAC-E2, Part 1 | t1/2 of E2 | 39.9 hours |
| Phase 3 NOMAC-E2, Part 1 | t1/2 of E2 | 39.1 hours |
| Commercial NOMAC-E2, Part 2 | t1/2 of E2 | 33.1 hours |
| Phase 3 NOMAC-E2, Part 2 | t1/2 of E2 | 34.6 hours |
Secondary
Terminal Phase Half Life (t1/2) of NOMAC
Time frame: 0 hours to t1/2 (blood samples were collected for NOMAC evaluation up to 144 hours postdose)
Population: The # of plasma profiles analyzed is based on the # of single-dose administration periods actually completed (some participants discontinued without completing all 4 dosing periods).~Part 1 analyses also excluded certain data from participants who were misdosed, and Part 2 analyses excluded participants who did not receive drug.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Commercial NOMAC-E2, Part 1 | Terminal Phase Half Life (t1/2) of NOMAC | 58.5 hours |
| Phase 3 NOMAC-E2, Part 1 | Terminal Phase Half Life (t1/2) of NOMAC | 61 hours |
| Commercial NOMAC-E2, Part 2 | Terminal Phase Half Life (t1/2) of NOMAC | 70.8 hours |
| Phase 3 NOMAC-E2, Part 2 | Terminal Phase Half Life (t1/2) of NOMAC | 69.9 hours |
Secondary
Tmax of E2
Time frame: 0 hours to tmax of E2 (blood samples were collected for E2 evaluation up to 96 hours postdose)
Population: The # of plasma profiles analyzed is based on the # of single-dose administration periods actually completed (some participants discontinued without completing all 4 dosing periods).~Part 1 analyses also excluded certain data from participants who were misdosed, and Part 2 analyses excluded participants who did not receive drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Commercial NOMAC-E2, Part 1 | Tmax of E2 | 6.02 hours |
| Phase 3 NOMAC-E2, Part 1 | Tmax of E2 | 8 hours |
| Commercial NOMAC-E2, Part 2 | Tmax of E2 | 8 hours |
| Phase 3 NOMAC-E2, Part 2 | Tmax of E2 | 8 hours |
Secondary
Tmax of NOMAC
Time frame: 0 hours to tmax of NOMAC (blood samples were collected for NOMAC evaluation up to 144 hours postdose)
Population: The # of plasma profiles analyzed is based on the # of single-dose administration periods actually completed (some participants discontinued without completing all 4 dosing periods).~Part 1 analyses also excluded certain data from participants who were misdosed, and Part 2 analyses excluded participants who did not receive drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Commercial NOMAC-E2, Part 1 | Tmax of NOMAC | 2 hours |
| Phase 3 NOMAC-E2, Part 1 | Tmax of NOMAC | 2 hours |
| Commercial NOMAC-E2, Part 2 | Tmax of NOMAC | 2 hours |
| Phase 3 NOMAC-E2, Part 2 | Tmax of NOMAC | 2 hours |
Secondary
Volume of Distribution (Calculated for NOMAC Only)
Time frame: blood samples were collected for NOMAC evaluation up to 144 hours postdose
Population: The # of plasma profiles analyzed is based on the # of single-dose administration periods actually completed (some participants discontinued without completing all 4 dosing periods).~Part 1 analyses also excluded certain data from participants who were misdosed, and Part 2 analyses excluded participants who did not receive drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Commercial NOMAC-E2, Part 1 | Volume of Distribution (Calculated for NOMAC Only) | 2208 L | Standard Deviation 886 |
| Phase 3 NOMAC-E2, Part 1 | Volume of Distribution (Calculated for NOMAC Only) | 2445 L | Standard Deviation 906 |
| Commercial NOMAC-E2, Part 2 | Volume of Distribution (Calculated for NOMAC Only) | 1988 L | Standard Deviation 631 |
| Phase 3 NOMAC-E2, Part 2 | Volume of Distribution (Calculated for NOMAC Only) | 2061 L | Standard Deviation 673 |