Trial Outcomes & Findings for Study to Evaluate the Safety, Tolerability and Pharmacokinetics of AMG 986 Administered Orally to Healthy Volunteers and Participants With Severely Impaired Renal Function (NCT NCT03318809)

NCT ID: NCT03318809

Last Updated: 2022-06-23

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 12 participants
• Primary outcome timeframe: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose
• Results posted on: 2022-06-23

Participant Flow

This study was conducted in 4 centers in the United States.

Participant milestones

Measure	Group 1: Severely Renal Impaired Participants Participants with severely impaired renal function (estimated glomerular filtration rate \[eGFR\] 15 to 29 mL/min/1.73 m\^2) received a single oral dose of 200 mg AMG 986.	Group 2: Healthy Participants Participants with normal renal function (eGFR \>= 90 mL/min/1.73 m\^2 or above) received a single oral dose of 200 mg AMG 986.
Overall Study STARTED	6	6
Overall Study COMPLETED	6	6
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study to Evaluate the Safety, Tolerability and Pharmacokinetics of AMG 986 Administered Orally to Healthy Volunteers and Participants With Severely Impaired Renal Function

Baseline characteristics by cohort

Measure	Group 1: Severely Renal Impaired Participants n=6 Participants Participants with severely impaired renal function (eGFR 15 to 29 mL/min/1.73 m\^2) received a single oral dose of 200 mg AMG 986.	Group 2: Healthy Participants n=6 Participants Participants with normal renal function (eGFR \>= 90 mL/min/1.73 m\^2 or above) received a single oral dose of 200 mg AMG 986.	Total n=12 Participants Total of all reporting groups
Sex: Female, Male Male	3 Participants n=93 Participants	3 Participants n=4 Participants	6 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Age, Continuous	56.7 years STANDARD_DEVIATION 8.1 • n=93 Participants	57.8 years STANDARD_DEVIATION 3.3 • n=4 Participants	57.3 years STANDARD_DEVIATION 5.9 • n=27 Participants
Sex: Female, Male Female	3 Participants n=93 Participants	3 Participants n=4 Participants	6 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=93 Participants	5 Participants n=4 Participants	11 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race/Ethnicity, Customized Asian	1 Participants n=93 Participants	1 Participants n=4 Participants	2 Participants n=27 Participants
Race/Ethnicity, Customized Black (or African American)	3 Participants n=93 Participants	3 Participants n=4 Participants	6 Participants n=27 Participants
Race/Ethnicity, Customized White	2 Participants n=93 Participants	2 Participants n=4 Participants	4 Participants n=27 Participants

PRIMARY outcome

Timeframe: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose

Population: The PK analysis set included all participants for whom at least 1 PK parameter or endpoint could be reliably estimated.

Outcome measures

Measure	Group 1: Severely Renal Impaired Participants n=6 Participants Participants with severely impaired renal function (eGFR 15 to 29 mL/min/1.73 m\^2) received a single oral dose of 200 mg AMG 986.	Group 2: Healthy Participants n=6 Participants Participants with normal renal function (eGFR \>= 90 mL/min/1.73 m\^2 or above) received a single oral dose of 200 mg AMG 986.
AMG 986 Pharmacokinetic (PK) Parameter: Area Under the Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Sample (AUClast)	80,000 hr*ng/mL Geometric Coefficient of Variation 33.6	64,500 hr*ng/mL Geometric Coefficient of Variation 70.0

PRIMARY outcome

Timeframe: 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose

Population: The PK analysis set included all participants for whom at least 1 PK parameter or endpoint could be reliably estimated.

Outcome measures

Measure	Group 1: Severely Renal Impaired Participants n=6 Participants Participants with severely impaired renal function (eGFR 15 to 29 mL/min/1.73 m\^2) received a single oral dose of 200 mg AMG 986.	Group 2: Healthy Participants n=6 Participants Participants with normal renal function (eGFR \>= 90 mL/min/1.73 m\^2 or above) received a single oral dose of 200 mg AMG 986.
AMG 986 PK Parameter: Maximum Observed Plasma Concentration After Dosing (Cmax)	10,600 ng/mL Geometric Coefficient of Variation 45.3	7520 ng/mL Geometric Coefficient of Variation 50.5

PRIMARY outcome

Timeframe: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose

Population: The PK analysis set included all participants for whom at least 1 PK parameter or endpoint could be reliably estimated.

Outcome measures

Measure	Group 1: Severely Renal Impaired Participants n=6 Participants Participants with severely impaired renal function (eGFR 15 to 29 mL/min/1.73 m\^2) received a single oral dose of 200 mg AMG 986.	Group 2: Healthy Participants n=6 Participants Participants with normal renal function (eGFR \>= 90 mL/min/1.73 m\^2 or above) received a single oral dose of 200 mg AMG 986.
AMG 986 PK Parameter: Terminal Phase Half-Life (t1/2,z)	18.4 hours Geometric Coefficient of Variation 21.1	21.1 hours Geometric Coefficient of Variation 44.6

PRIMARY outcome

Timeframe: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose

Population: The PK analysis set included all participants for whom at least 1 PK parameter or endpoint could be reliably estimated.

Outcome measures

Measure	Group 1: Severely Renal Impaired Participants n=6 Participants Participants with severely impaired renal function (eGFR 15 to 29 mL/min/1.73 m\^2) received a single oral dose of 200 mg AMG 986.	Group 2: Healthy Participants n=6 Participants Participants with normal renal function (eGFR \>= 90 mL/min/1.73 m\^2 or above) received a single oral dose of 200 mg AMG 986.
AMG 986 PK Parameter: Time of Maximum Plasma Concentration (Tmax)	1.1 hours Interval 1.0 to 2.1	1.5 hours Interval 1.1 to 4.1

PRIMARY outcome

Timeframe: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose

Population: The PK analysis set included all participants for whom at least 1 PK parameter or endpoint could be reliably estimated.

Outcome measures

Measure	Group 1: Severely Renal Impaired Participants n=6 Participants Participants with severely impaired renal function (eGFR 15 to 29 mL/min/1.73 m\^2) received a single oral dose of 200 mg AMG 986.	Group 2: Healthy Participants n=6 Participants Participants with normal renal function (eGFR \>= 90 mL/min/1.73 m\^2 or above) received a single oral dose of 200 mg AMG 986.
AMG 986 PK Parameter: Area Under the Plasma Concentration Time Curve From Time 0 to Infinity (AUCinf)	80,800 ng*hr/mL Geometric Coefficient of Variation 33.6	65,800 ng*hr/mL Geometric Coefficient of Variation 68.8

SECONDARY outcome

Timeframe: From first dose of study drug up to Day 30

Population: The safety analysis set included all study participants who received at least 1 dose of AMG 986.

An adverse event is defined as any untoward medical occurrence in a clinical trial subject. A serious adverse event is defined as an adverse event that meets at least 1 of the following serious criteria:

• fatal
• life threatening (places the subject at immediate risk of death)
• requires in patient hospitalization or prolongation of existing hospitalization
• results in persistent or significant disability/incapacity
• congenital anomaly/birth defect
• other medically important serious event

Outcome measures

Measure	Group 1: Severely Renal Impaired Participants n=6 Participants Participants with severely impaired renal function (eGFR 15 to 29 mL/min/1.73 m\^2) received a single oral dose of 200 mg AMG 986.	Group 2: Healthy Participants n=6 Participants Participants with normal renal function (eGFR \>= 90 mL/min/1.73 m\^2 or above) received a single oral dose of 200 mg AMG 986.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) TEAEs	2 participants	1 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Serious TEAEs	0 participants	0 participants

Adverse Events

Group 1: Severely Renal Impaired Participants

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Group 2: Healthy Participants

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Group 1: Severely Renal Impaired Participants n=6 participants at risk Participants with severely impaired renal function (eGFR 15 to 29 mL/min/1.73 m\^2) received a single oral dose of 200 mg AMG 986.	Group 2: Healthy Participants n=6 participants at risk Participants with normal renal function (eGFR \>= 90 mL/min/1.73 m\^2 or above) received a single oral dose of 200 mg AMG 986.
Gastrointestinal disorders Nausea	0.00% 0/6 • From first dose of study drug up to Day 30	16.7% 1/6 • From first dose of study drug up to Day 30
Nervous system disorders Dizziness	0.00% 0/6 • From first dose of study drug up to Day 30	16.7% 1/6 • From first dose of study drug up to Day 30
Nervous system disorders Headache	16.7% 1/6 • From first dose of study drug up to Day 30	0.00% 0/6 • From first dose of study drug up to Day 30
Respiratory, thoracic and mediastinal disorders Dyspnoea	16.7% 1/6 • From first dose of study drug up to Day 30	0.00% 0/6 • From first dose of study drug up to Day 30

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