Trial Outcomes & Findings for Study to Evaluate the Pharmacokinetics of Single and Multiple Doses of Apremilast in Healthy Adult Male Korean Subjects (NCT NCT02802735)

NCT ID: NCT02802735

Last Updated: 2021-07-06

Results Overview

Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 28 participants
• Primary outcome timeframe: Day 1 of each treatment period at predose (0 hour) and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60, and 72 hours post-dose.
• Results posted on: 2021-07-06

Participant Flow

This was a two-part study in healthy Korean men. The study was conducted at 1 clinic in Korea.

In Part 1 participants were randomized to 1 of 3 treatment sequences consisting of 3 treatment periods. In Part 2 participants were randomized in a 3:1 ratio to receive apremilast or matching placebo twice a day (BID) for 14 days.

Participant milestones

Measure	Part 1: Apremilast 20 mg / 30 mg / 40 mg Participants received a single oral dose of 20 mg apremilast on day 1 of period 1, a single oral dose of 30 mg apremilast on day 1 of period 2, and a single oral dose of 40 mg apremilast on day 1 of period 3. There was a 7-10 day washout period between each dose.	Part 1: Apremilast 30 mg / 20 mg / 40 mg Participants received a single oral dose of 30 mg apremilast on day 1 of period 1, a single oral dose of 20 mg apremilast on day 1 of period 2, and a single oral dose of 40 mg apremilast on day 1 of period 3. There was a 7-10 day washout period between each dose.	Part 1: Apremilast 40 mg / 20 mg / 30 mg Participants received a single oral dose of 40 mg apremilast on day 1 of period 1, a single oral dose of 20 mg apremilast on day 1 of period 2, and a single oral dose of 30 mg apremilast on day 1 of period 3. There was a 7-10 day washout period between each dose.	Part 2: Apremilast 30 mg BID Participants received 30 mg apremilast orally twice a day for 14 days.	Part 2: Placebo BID Participants received matching placebo orally twice a day for 14 days.
Overall Study STARTED	4	4	4	12	4
Overall Study COMPLETED	4	3	4	12	4
Overall Study NOT COMPLETED	0	1	0	0	0

Reasons for withdrawal

Measure	Part 1: Apremilast 20 mg / 30 mg / 40 mg Participants received a single oral dose of 20 mg apremilast on day 1 of period 1, a single oral dose of 30 mg apremilast on day 1 of period 2, and a single oral dose of 40 mg apremilast on day 1 of period 3. There was a 7-10 day washout period between each dose.	Part 1: Apremilast 30 mg / 20 mg / 40 mg Participants received a single oral dose of 30 mg apremilast on day 1 of period 1, a single oral dose of 20 mg apremilast on day 1 of period 2, and a single oral dose of 40 mg apremilast on day 1 of period 3. There was a 7-10 day washout period between each dose.	Part 1: Apremilast 40 mg / 20 mg / 30 mg Participants received a single oral dose of 40 mg apremilast on day 1 of period 1, a single oral dose of 20 mg apremilast on day 1 of period 2, and a single oral dose of 30 mg apremilast on day 1 of period 3. There was a 7-10 day washout period between each dose.	Part 2: Apremilast 30 mg BID Participants received 30 mg apremilast orally twice a day for 14 days.	Part 2: Placebo BID Participants received matching placebo orally twice a day for 14 days.
Overall Study Withdrawal by Subject	0	1	0	0	0

Baseline Characteristics

Study to Evaluate the Pharmacokinetics of Single and Multiple Doses of Apremilast in Healthy Adult Male Korean Subjects

Baseline characteristics by cohort

Measure	Part 1: Apremilast n=12 Participants Participants received a single oral dose of 20 mg apremilast, 30 mg apremilast, and 40 mg apremilast across 3 treatment periods separated by a washout period of 7-10 days.	Part 2: Apremilast 30 mg BID n=12 Participants Participants received 30 mg apremilast orally twice a day for 14 days.	Part 2: Placebo BID n=4 Participants Participants received matching placebo orally twice a day for 14 days.	Total n=28 Participants Total of all reporting groups
Age, Continuous	29.8 years n=5 Participants	30.8 years n=7 Participants	25.5 years n=5 Participants	29.6 years n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	12 Participants n=7 Participants	4 Participants n=5 Participants	28 Participants n=4 Participants
Race/Ethnicity, Customized Asian	12 Participants n=5 Participants	12 Participants n=7 Participants	4 Participants n=5 Participants	28 Participants n=4 Participants

PRIMARY outcome

Timeframe: Day 1 of each treatment period at predose (0 hour) and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60, and 72 hours post-dose.

Population: Participants who received at least 1 dose of apremilast and had at least 1 measurable concentration datum.

Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.

Outcome measures

Measure	Part 1: Apremilast 20 mg n=11 Participants Participants received a single oral dose of 20 mg apremilast.	Part 1: Apremilast 30 mg n=12 Participants Participants received a single oral dose of 30 mg apremilast.	Part 1: Apremilast 40 mg n=12 Participants Participants received a single oral dose of 40 mg apremilast.	Part 2: Apremilast 30 mg BID Participants received 30 mg apremilast orally twice a day for 14 days.	Part 2: Placebo BID Participants received matching placebo orally twice a day for 14 days.
Part 1: Maximum Observed Plasma Concentration (Cmax) of Apremilast	205 ng/mL Geometric Coefficient of Variation 32.1	273 ng/mL Geometric Coefficient of Variation 32.1	373 ng/mL Geometric Coefficient of Variation 19.7	—	—

PRIMARY outcome

Timeframe: Day 1 of each treatment period at predose (0 hour) and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60, and 72 hours post-dose.

Population: Participants who received at least 1 dose of apremilast and had at least 1 measurable concentration datum.

Outcome measures

Measure	Part 1: Apremilast 20 mg n=11 Participants Participants received a single oral dose of 20 mg apremilast.	Part 1: Apremilast 30 mg n=12 Participants Participants received a single oral dose of 30 mg apremilast.	Part 1: Apremilast 40 mg n=12 Participants Participants received a single oral dose of 40 mg apremilast.	Part 2: Apremilast 30 mg BID Participants received 30 mg apremilast orally twice a day for 14 days.	Part 2: Placebo BID Participants received matching placebo orally twice a day for 14 days.
Part 1: Time to Maximum Observed Plasma Concentration (Tmax) of Apremilast	3.0 hours Interval 1.5 to 5.0	3.0 hours Interval 1.5 to 5.0	2.0 hours Interval 0.5 to 5.0	—	—

PRIMARY outcome

Timeframe: Day 1 of each treatment period at predose (0 hour) and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60, and 72 hours post-dose.

Population: Participants who received at least 1 dose of apremilast and had at least 1 measurable concentration datum.

Outcome measures

Measure	Part 1: Apremilast 20 mg n=11 Participants Participants received a single oral dose of 20 mg apremilast.	Part 1: Apremilast 30 mg n=12 Participants Participants received a single oral dose of 30 mg apremilast.	Part 1: Apremilast 40 mg n=12 Participants Participants received a single oral dose of 40 mg apremilast.	Part 2: Apremilast 30 mg BID Participants received 30 mg apremilast orally twice a day for 14 days.	Part 2: Placebo BID Participants received matching placebo orally twice a day for 14 days.
Part 1: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-t) for Apremilast	1770 ng*hr/mL Geometric Coefficient of Variation 25.8	2330 ng*hr/mL Geometric Coefficient of Variation 22.6	3470 ng*hr/mL Geometric Coefficient of Variation 25.7	—	—

PRIMARY outcome

Timeframe: Day 1 of each treatment period at predose (0 hour) and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60, and 72 hours post-dose.

Population: Participants who received at least 1 dose of apremilast and had at least 1 measurable concentration datum.

Outcome measures

Measure	Part 1: Apremilast 20 mg n=11 Participants Participants received a single oral dose of 20 mg apremilast.	Part 1: Apremilast 30 mg n=12 Participants Participants received a single oral dose of 30 mg apremilast.	Part 1: Apremilast 40 mg n=12 Participants Participants received a single oral dose of 40 mg apremilast.	Part 2: Apremilast 30 mg BID Participants received 30 mg apremilast orally twice a day for 14 days.	Part 2: Placebo BID Participants received matching placebo orally twice a day for 14 days.
Part 1: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) for Apremilast	1790 ng*hr/mL Geometric Coefficient of Variation 25.5	2360 ng*hr/mL Geometric Coefficient of Variation 22.1	3500 ng*hr/mL Geometric Coefficient of Variation 25.6	—	—

PRIMARY outcome

Timeframe: Day 1 of each treatment period at predose (0 hour) and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60, and 72 hours post-dose.

Population: Participants who received at least 1 dose of apremilast and had at least 1 measurable concentration datum.

Outcome measures

Measure	Part 1: Apremilast 20 mg n=11 Participants Participants received a single oral dose of 20 mg apremilast.	Part 1: Apremilast 30 mg n=12 Participants Participants received a single oral dose of 30 mg apremilast.	Part 1: Apremilast 40 mg n=12 Participants Participants received a single oral dose of 40 mg apremilast.	Part 2: Apremilast 30 mg BID Participants received 30 mg apremilast orally twice a day for 14 days.	Part 2: Placebo BID Participants received matching placebo orally twice a day for 14 days.
Part 1: Terminal Elimination Half-life (T1/2) for Apremilast	7.4 hours Geometric Coefficient of Variation 35.2	8.2 hours Geometric Coefficient of Variation 44.4	7.4 hours Geometric Coefficient of Variation 36.8	—	—

PRIMARY outcome

Timeframe: Day 1 of each treatment period at predose (0 hour) and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60, and 72 hours post-dose.

Population: Participants who received at least 1 dose of apremilast and had at least 1 measurable concentration datum.

Outcome measures

Measure	Part 1: Apremilast 20 mg n=11 Participants Participants received a single oral dose of 20 mg apremilast.	Part 1: Apremilast 30 mg n=12 Participants Participants received a single oral dose of 30 mg apremilast.	Part 1: Apremilast 40 mg n=12 Participants Participants received a single oral dose of 40 mg apremilast.	Part 2: Apremilast 30 mg BID Participants received 30 mg apremilast orally twice a day for 14 days.	Part 2: Placebo BID Participants received matching placebo orally twice a day for 14 days.
Part 1: Apparent Clearance of Apremilast From Plasma After Extravascular Administration (CL/F)	11.1 liters/hour Geometric Coefficient of Variation 25.5	12.7 liters/hour Geometric Coefficient of Variation 22.1	11.4 liters/hour Geometric Coefficient of Variation 25.6	—	—

PRIMARY outcome

Timeframe: Day 1 of each treatment period at predose (0 hour) and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60, and 72 hours post-dose.

Population: Participants who received at least 1 dose of apremilast and had at least 1 measurable concentration datum.

Outcome measures

Measure	Part 1: Apremilast 20 mg n=11 Participants Participants received a single oral dose of 20 mg apremilast.	Part 1: Apremilast 30 mg n=12 Participants Participants received a single oral dose of 30 mg apremilast.	Part 1: Apremilast 40 mg n=12 Participants Participants received a single oral dose of 40 mg apremilast.	Part 2: Apremilast 30 mg BID Participants received 30 mg apremilast orally twice a day for 14 days.	Part 2: Placebo BID Participants received matching placebo orally twice a day for 14 days.
Part 1: Apparent Volume of Distribution of Apremilast During the Terminal Phase (Vz/F)	120 liters Geometric Coefficient of Variation 47.6	151 liters Geometric Coefficient of Variation 49.6	122 liters Geometric Coefficient of Variation 38.7	—	—

PRIMARY outcome

Timeframe: Day 1 and day 14 prior to the morning dose (0 hour), and at 0.5, 1, 1.5, 2, 3, 5, 8, and 12 hours after the morning dose

Population: Participants who received at least 1 dose of apremilast and had at least 1 measurable concentration datum.

Area under the plasma concentration-time curve during a dosage interval (tau) at steady state, where tau is 12 hours.

Outcome measures

Measure	Part 1: Apremilast 20 mg n=12 Participants Participants received a single oral dose of 20 mg apremilast.	Part 1: Apremilast 30 mg Participants received a single oral dose of 30 mg apremilast.	Part 1: Apremilast 40 mg Participants received a single oral dose of 40 mg apremilast.	Part 2: Apremilast 30 mg BID Participants received 30 mg apremilast orally twice a day for 14 days.	Part 2: Placebo BID Participants received matching placebo orally twice a day for 14 days.
Part 2: Area Under the Plasma Concentration-time Curve During a Dosage Interval (AUCτ) for Apremilast Day 1	1610 ng*hr/mL Geometric Coefficient of Variation 33.0	—	—	—	—
Part 2: Area Under the Plasma Concentration-time Curve During a Dosage Interval (AUCτ) for Apremilast Day 14	2600 ng*hr/mL Geometric Coefficient of Variation 34.3	—	—	—	—

PRIMARY outcome

Timeframe: Day 1 and day 14 prior to the morning dose (0 hour), and at 0.5, 1, 1.5, 2, 3, 5, 8, and 12 hours after the morning dose

Population: Participants who received at least 1 dose of apremilast and had at least 1 measurable concentration datum.

Outcome measures

Measure	Part 1: Apremilast 20 mg n=12 Participants Participants received a single oral dose of 20 mg apremilast.	Part 1: Apremilast 30 mg Participants received a single oral dose of 30 mg apremilast.	Part 1: Apremilast 40 mg Participants received a single oral dose of 40 mg apremilast.	Part 2: Apremilast 30 mg BID Participants received 30 mg apremilast orally twice a day for 14 days.	Part 2: Placebo BID Participants received matching placebo orally twice a day for 14 days.
Part 2: Maximum Observed Plasma Concentration (Cmax) of Apremilast Day 1	283 ng/mL Geometric Coefficient of Variation 34.3	—	—	—	—
Part 2: Maximum Observed Plasma Concentration (Cmax) of Apremilast Day 14	408 ng/mL Geometric Coefficient of Variation 36.5	—	—	—	—

PRIMARY outcome

Timeframe: Day 1 and day 14 prior to the morning dose (0 hour), and at 0.5, 1, 1.5, 2, 3, 5, 8, and 12 hours after the morning dose

Population: Participants who received at least 1 dose of apremilast and had at least 1 measurable concentration datum.

Outcome measures

Measure	Part 1: Apremilast 20 mg n=12 Participants Participants received a single oral dose of 20 mg apremilast.	Part 1: Apremilast 30 mg Participants received a single oral dose of 30 mg apremilast.	Part 1: Apremilast 40 mg Participants received a single oral dose of 40 mg apremilast.	Part 2: Apremilast 30 mg BID Participants received 30 mg apremilast orally twice a day for 14 days.	Part 2: Placebo BID Participants received matching placebo orally twice a day for 14 days.
Part 2: Time to Maximum Observed Plasma Concentration (Tmax) of Apremilast Day 1	2.00 hours Interval 1.0 to 5.0	—	—	—	—
Part 2: Time to Maximum Observed Plasma Concentration (Tmax) of Apremilast Day 14	1.50 hours Interval 1.0 to 3.0	—	—	—	—

PRIMARY outcome

Timeframe: Day 14 prior to the morning dose (0 hour), and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60, and 72 hours after the morning dose

Population: Participants who received at least 1 dose of apremilast and had at least 1 measurable concentration datum.

Outcome measures

Measure	Part 1: Apremilast 20 mg n=12 Participants Participants received a single oral dose of 20 mg apremilast.	Part 1: Apremilast 30 mg Participants received a single oral dose of 30 mg apremilast.	Part 1: Apremilast 40 mg Participants received a single oral dose of 40 mg apremilast.	Part 2: Apremilast 30 mg BID Participants received 30 mg apremilast orally twice a day for 14 days.	Part 2: Placebo BID Participants received matching placebo orally twice a day for 14 days.
Part 2: Terminal Elimination Half-life (T1/2) for Apremilast	7.80 hours Geometric Coefficient of Variation 31.4	—	—	—	—

PRIMARY outcome

Timeframe: Day 14 prior to the morning dose (0 hour), and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60, and 72 hours after the morning dose

Population: Participants who received at least 1 dose of apremilast and had at least 1 measurable concentration datum.

Outcome measures

Measure	Part 1: Apremilast 20 mg n=12 Participants Participants received a single oral dose of 20 mg apremilast.	Part 1: Apremilast 30 mg Participants received a single oral dose of 30 mg apremilast.	Part 1: Apremilast 40 mg Participants received a single oral dose of 40 mg apremilast.	Part 2: Apremilast 30 mg BID Participants received 30 mg apremilast orally twice a day for 14 days.	Part 2: Placebo BID Participants received matching placebo orally twice a day for 14 days.
Part 2: Apparent Clearance of Apremilast From Plasma After Extravascular Administration (CL/F)	11.5 liters/hour Geometric Coefficient of Variation 34.3	—	—	—	—

PRIMARY outcome

Timeframe: Day 14 prior to the morning dose (0 hour), and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60, and 72 hours after the morning dose

Population: Participants who received at least 1 dose of apremilast and had at least 1 measurable concentration datum.

Outcome measures

Measure	Part 1: Apremilast 20 mg n=12 Participants Participants received a single oral dose of 20 mg apremilast.	Part 1: Apremilast 30 mg Participants received a single oral dose of 30 mg apremilast.	Part 1: Apremilast 40 mg Participants received a single oral dose of 40 mg apremilast.	Part 2: Apremilast 30 mg BID Participants received 30 mg apremilast orally twice a day for 14 days.	Part 2: Placebo BID Participants received matching placebo orally twice a day for 14 days.
Part 2: Apparent Volume of Distribution of Apremilast During the Terminal Phase (Vz/F)	130 liters Geometric Coefficient of Variation 53.3	—	—	—	—

PRIMARY outcome

Timeframe: Day 1 and day 14 prior to the morning dose (0 hour), and at 0.5, 1, 1.5, 2, 3, 5, 8, and 12 hours after the morning dose, and on day 14 only at 24, 36, 48, 60, and 72 hours after the morning dose

Population: Participants who received at least 1 dose of apremilast and had at least 1 measurable concentration datum.

Ratio of accumulation calculated as Day 14 AUC0-τ / Day 1 AUC0-τ

Outcome measures

Measure	Part 1: Apremilast 20 mg n=12 Participants Participants received a single oral dose of 20 mg apremilast.	Part 1: Apremilast 30 mg Participants received a single oral dose of 30 mg apremilast.	Part 1: Apremilast 40 mg Participants received a single oral dose of 40 mg apremilast.	Part 2: Apremilast 30 mg BID Participants received 30 mg apremilast orally twice a day for 14 days.	Part 2: Placebo BID Participants received matching placebo orally twice a day for 14 days.
Part 2: Ratio of Accumulation	1.62 ratio Geometric Coefficient of Variation 36.0	—	—	—	—

SECONDARY outcome

Timeframe: Part 1, up to 40 days; Part 2, up to 24 days

Population: Participants who received at least 1 dose of apremilast.

Outcome measures

Measure	Part 1: Apremilast 20 mg n=11 Participants Participants received a single oral dose of 20 mg apremilast.	Part 1: Apremilast 30 mg n=12 Participants Participants received a single oral dose of 30 mg apremilast.	Part 1: Apremilast 40 mg n=12 Participants Participants received a single oral dose of 40 mg apremilast.	Part 2: Apremilast 30 mg BID n=12 Participants Participants received 30 mg apremilast orally twice a day for 14 days.	Part 2: Placebo BID n=4 Participants Participants received matching placebo orally twice a day for 14 days.
Number of Participants With Treatment-emergent Adverse Events (AEs) Serious adverse events	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events (AEs) Any treatment-emergent adverse event (TEAE)	2 Participants	1 Participants	3 Participants	7 Participants	3 Participants
Number of Participants With Treatment-emergent Adverse Events (AEs) TEAE related to study drug	1 Participants	1 Participants	2 Participants	6 Participants	2 Participants
Number of Participants With Treatment-emergent Adverse Events (AEs) Serious adverse events related o study dug	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events (AEs) TEAE leading to discontinuation	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events (AEs) Treatment-related TEAE leading to discontinuation	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events (AEs) Deaths	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

Adverse Events

Part 1: Apremilast 20 mg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Part 1: Apremilast 30 mg

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Part 1: Apremilast 40 mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Part 1: Total

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Part 2: Apremilast 30 mg BID

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Part 2: Placebo BID

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Part 2: Total

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Part 1: Apremilast 20 mg n=11 participants at risk Participants received a single oral dose of 20 mg apremilast.	Part 1: Apremilast 30 mg n=12 participants at risk Participants received a single oral dose of 30 mg apremilast.	Part 1: Apremilast 40 mg n=12 participants at risk Participants received a single oral dose of 40 mg apremilast.	Part 1: Total n=12 participants at risk Participants received a single oral dose of 20 mg apremilast, 30 mg apremilast, and 40 mg apremilast across 3 treatment periods separated by a washout period of 7-10 days.	Part 2: Apremilast 30 mg BID n=12 participants at risk Participants received 30 mg apremilast orally twice a day for 14 days.	Part 2: Placebo BID n=4 participants at risk Participants received matching placebo orally twice a day for 14 days.	Part 2: Total n=16 participants at risk Participants who received 30 mg apremilast or placebo twice a day for 14 days
Gastrointestinal disorders Abdominal pain upper	0.00% 0/11 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/12 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/12 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/12 • Part 1, up to 40 days; Part 2, up to 24 days	8.3% 1/12 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/4 • Part 1, up to 40 days; Part 2, up to 24 days	6.2% 1/16 • Part 1, up to 40 days; Part 2, up to 24 days
Gastrointestinal disorders Diarrhoea	9.1% 1/11 • Part 1, up to 40 days; Part 2, up to 24 days	8.3% 1/12 • Part 1, up to 40 days; Part 2, up to 24 days	8.3% 1/12 • Part 1, up to 40 days; Part 2, up to 24 days	8.3% 1/12 • Part 1, up to 40 days; Part 2, up to 24 days	16.7% 2/12 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/4 • Part 1, up to 40 days; Part 2, up to 24 days	12.5% 2/16 • Part 1, up to 40 days; Part 2, up to 24 days
Gastrointestinal disorders Nausea	0.00% 0/11 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/12 • Part 1, up to 40 days; Part 2, up to 24 days	16.7% 2/12 • Part 1, up to 40 days; Part 2, up to 24 days	16.7% 2/12 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/12 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/4 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/16 • Part 1, up to 40 days; Part 2, up to 24 days
Infections and infestations Upper respiratory tract infection	0.00% 0/11 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/12 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/12 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/12 • Part 1, up to 40 days; Part 2, up to 24 days	25.0% 3/12 • Part 1, up to 40 days; Part 2, up to 24 days	25.0% 1/4 • Part 1, up to 40 days; Part 2, up to 24 days	25.0% 4/16 • Part 1, up to 40 days; Part 2, up to 24 days
Injury, poisoning and procedural complications Skin abrasion	0.00% 0/11 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/12 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/12 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/12 • Part 1, up to 40 days; Part 2, up to 24 days	8.3% 1/12 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/4 • Part 1, up to 40 days; Part 2, up to 24 days	6.2% 1/16 • Part 1, up to 40 days; Part 2, up to 24 days
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/11 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/12 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/12 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/12 • Part 1, up to 40 days; Part 2, up to 24 days	8.3% 1/12 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/4 • Part 1, up to 40 days; Part 2, up to 24 days	6.2% 1/16 • Part 1, up to 40 days; Part 2, up to 24 days
Nervous system disorders Headache	0.00% 0/11 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/12 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/12 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/12 • Part 1, up to 40 days; Part 2, up to 24 days	33.3% 4/12 • Part 1, up to 40 days; Part 2, up to 24 days	25.0% 1/4 • Part 1, up to 40 days; Part 2, up to 24 days	31.2% 5/16 • Part 1, up to 40 days; Part 2, up to 24 days
Respiratory, thoracic and mediastinal disorders Epistaxis	9.1% 1/11 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/12 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/12 • Part 1, up to 40 days; Part 2, up to 24 days	8.3% 1/12 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/12 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/4 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/16 • Part 1, up to 40 days; Part 2, up to 24 days
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/11 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/12 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/12 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/12 • Part 1, up to 40 days; Part 2, up to 24 days	8.3% 1/12 • Part 1, up to 40 days; Part 2, up to 24 days	25.0% 1/4 • Part 1, up to 40 days; Part 2, up to 24 days	12.5% 2/16 • Part 1, up to 40 days; Part 2, up to 24 days
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/11 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/12 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/12 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/12 • Part 1, up to 40 days; Part 2, up to 24 days	8.3% 1/12 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/4 • Part 1, up to 40 days; Part 2, up to 24 days	6.2% 1/16 • Part 1, up to 40 days; Part 2, up to 24 days
Skin and subcutaneous tissue disorders Rash	0.00% 0/11 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/12 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/12 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/12 • Part 1, up to 40 days; Part 2, up to 24 days	8.3% 1/12 • Part 1, up to 40 days; Part 2, up to 24 days	25.0% 1/4 • Part 1, up to 40 days; Part 2, up to 24 days	12.5% 2/16 • Part 1, up to 40 days; Part 2, up to 24 days
Skin and subcutaneous tissue disorders Rash papular	0.00% 0/11 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/12 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/12 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/12 • Part 1, up to 40 days; Part 2, up to 24 days	8.3% 1/12 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/4 • Part 1, up to 40 days; Part 2, up to 24 days	6.2% 1/16 • Part 1, up to 40 days; Part 2, up to 24 days
Skin and subcutaneous tissue disorders Skin exfoliation	9.1% 1/11 • Part 1, up to 40 days; Part 2, up to 24 days	8.3% 1/12 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/12 • Part 1, up to 40 days; Part 2, up to 24 days	8.3% 1/12 • Part 1, up to 40 days; Part 2, up to 24 days	8.3% 1/12 • Part 1, up to 40 days; Part 2, up to 24 days	0.00% 0/4 • Part 1, up to 40 days; Part 2, up to 24 days	6.2% 1/16 • Part 1, up to 40 days; Part 2, up to 24 days

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Email: medinfo@amgen.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
• Publication restrictions are in place

Restriction type: OTHER