Trial Outcomes & Findings for Lipid Biomarker Study in Men With Dyslipidemia After Simvastatin Treatment (Study MK-0000-140)(COMPLETED) (NCT NCT00935259)

Last Updated: 2015-10-08

Results Overview

Arachidonic acid level (20:4n6) in the cholesterol ester lipid class. The mean reported was an adjusted mean, which was obtained from running a 2-period crossover model that had fixed treatment and period terms and a random participant term.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

31 participants

Primary outcome timeframe

2 weeks

Results posted on

2015-10-08

Participant Flow

Participant milestones

Participant milestones
Measure	Simvastatin 40 mg, Then Placebo Simvastatin 40 mg once daily for 2 weeks followed by placebo once daily for 2 weeks	Placebo First, Then Simvastatin 40 mg Placebo once daily for 2 weeks followed by simvastatin 40 mg daily for 2 weeks
Period 1 STARTED	16	15
Period 1 COMPLETED	15	14
Period 1 NOT COMPLETED	1	1
Period 2 STARTED	15	14
Period 2 COMPLETED	15	14
Period 2 NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Simvastatin 40 mg, Then Placebo Simvastatin 40 mg once daily for 2 weeks followed by placebo once daily for 2 weeks	Placebo First, Then Simvastatin 40 mg Placebo once daily for 2 weeks followed by simvastatin 40 mg daily for 2 weeks
Period 1 Administrative (scheduling conflict)	1	1

Baseline Characteristics

Lipid Biomarker Study in Men With Dyslipidemia After Simvastatin Treatment (Study MK-0000-140)(COMPLETED)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Participants n=31 Participants All enrolled participants
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	31 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	31 Participants n=5 Participants

PRIMARY outcome

Timeframe: 2 weeks

Population: Only participants with complete arachidonic acid data were included.

Outcome measures

Outcome measures
Measure	Simvastatin 40 mg n=27 Participants Simvastatin 40 mg once daily for 2 weeks followed by placebo once daily for 2 weeks	Placebo n=29 Participants Placebo once daily for 2 weeks followed by simvastatin 40 mg daily for 2 weeks
Arachidonic Acid Level After 2 Weeks of Treatment	259.1 nmol Standard Deviation 89.1	269.6 nmol Standard Deviation 85.2

SECONDARY outcome

Timeframe: 2 weeks

Population: Only participants with complete blood lipidomic data were included. For cholesterol ester 22:5n6, n=26 for the simvastatin arm and n=27 for the placebo arm.

Change in fasting blood cholesterol ester, lysophosphatidylcholine, phosphatidylcholine, phosphatidylethanolamine, and triacylglycerol levels compared to placebo. The mean reported was an adjusted mean.

Outcome measures

Outcome measures
Measure	Simvastatin 40 mg n=27 Participants Simvastatin 40 mg once daily for 2 weeks followed by placebo once daily for 2 weeks	Placebo n=29 Participants Placebo once daily for 2 weeks followed by simvastatin 40 mg daily for 2 weeks
Fasting Blood Lipidomic Levels After 2 Weeks of Treatment Cholesterol ester lipid 16:00	288.9 nmol Standard Deviation 102.1	345.1 nmol Standard Deviation 87.3
Fasting Blood Lipidomic Levels After 2 Weeks of Treatment Cholesterol ester lipid 18:3n3	10.0 nmol Standard Deviation 4.8	14.4 nmol Standard Deviation 6.7
Fasting Blood Lipidomic Levels After 2 Weeks of Treatment Cholesterol ester lipid 20:3n6	20.9 nmol Standard Deviation 10.5	23.5 nmol Standard Deviation 10.2
Fasting Blood Lipidomic Levels After 2 Weeks of Treatment Cholesterol ester lipid 20:3n9	1.3 nmol Standard Deviation 1.1	1.2 nmol Standard Deviation 0.9
Fasting Blood Lipidomic Levels After 2 Weeks of Treatment Cholesterol ester lipid 22:5n6	1.0 nmol Standard Deviation 0.8	1.1 nmol Standard Deviation 0.4
Fasting Blood Lipidomic Levels After 2 Weeks of Treatment Cholesterol ester lipid 22:6n3	12.7 nmol Standard Deviation 5.1	14.8 nmol Standard Deviation 6.8
Fasting Blood Lipidomic Levels After 2 Weeks of Treatment Lysophosphatidyl-choline lipid 20:4n6	11.1 nmol Standard Deviation 3.8	10.3 nmol Standard Deviation 2.7
Fasting Blood Lipidomic Levels After 2 Weeks of Treatment Phosphatidyl-choline lipid 18:2n6	684.8 nmol Standard Deviation 224.9	824.9 nmol Standard Deviation 196.2
Fasting Blood Lipidomic Levels After 2 Weeks of Treatment Phosphatidyl-choline lipid 20:3n6	117.4 nmol Standard Deviation 54.3	127.1 nmol Standard Deviation 58.8
Fasting Blood Lipidomic Levels After 2 Weeks of Treatment Phosphatidyl-choline lipid 20:4n6	458.0 nmol Standard Deviation 138.4	443.2 nmol Standard Deviation 98.1
Fasting Blood Lipidomic Levels After 2 Weeks of Treatment Phosphatidyl-choline lipid 22:5n3	30.3 nmol Standard Deviation 10.2	34.3 nmol Standard Deviation 12.8
Fasting Blood Lipidomic Levels After 2 Weeks of Treatment Phosphatidyl-choline lipid 22:5n6	11.4 nmol Standard Deviation 6.4	12.1 nmol Standard Deviation 4.1
Fasting Blood Lipidomic Levels After 2 Weeks of Treatment Phosphatidyl-ethanolamine lipid 18:2n6	21.8 nmol Standard Deviation 9.3	32.1 nmol Standard Deviation 15.5
Fasting Blood Lipidomic Levels After 2 Weeks of Treatment Triacylglycerol 16:00	788.3 nmol Standard Deviation 431.6	1005.1 nmol Standard Deviation 662.2
Fasting Blood Lipidomic Levels After 2 Weeks of Treatment Triacylglycerol 20:3n9	4.5 nmol Standard Deviation 5.5	4.9 nmol Standard Deviation 2.8

SECONDARY outcome

Timeframe: 2 weeks

Population: Only participants with complete PCSK9 data were included.

Two days of standardized, pre-packaged meals were provided prior to the 10-hour fast required before blood collection. To assess how consumption of a meal would affect levels of plasma PCSK9, following each of the fasting blood draws, participants were asked to consume a high fat meal (heavy whipping cream + vanilla ice cream in a 1:4 ratio \[dose = 162 g/m\^2\]) within 20 minutes. For the duration of the test, participants were to remain seated or recumbent until blood samples were drawn 4 h after meal completion. The mean reported was an adjusted mean (defined in first outcome measure).

Outcome measures

Outcome measures
Measure	Simvastatin 40 mg n=27 Participants Simvastatin 40 mg once daily for 2 weeks followed by placebo once daily for 2 weeks	Placebo n=29 Participants Placebo once daily for 2 weeks followed by simvastatin 40 mg daily for 2 weeks
Serum Proprotein Convertase Subtilisin-like/Kexin Type 9 (PCSK9) Level Fed	6.06 nmol Standard Deviation 2.34	4.69 nmol Standard Deviation 1.66
Serum Proprotein Convertase Subtilisin-like/Kexin Type 9 (PCSK9) Level Fasted	6.47 nmol Standard Deviation 2.11	5.51 nmol Standard Deviation 1.91

SECONDARY outcome

Timeframe: 2 weeks

Population: Only participants with complete blood linoleic acid data were included.

Change in blood linoleic acid levels for Cholesterol Ester compared to placebo.

Outcome measures

Outcome measures
Measure	Simvastatin 40 mg n=27 Participants Simvastatin 40 mg once daily for 2 weeks followed by placebo once daily for 2 weeks	Placebo n=29 Participants Placebo once daily for 2 weeks followed by simvastatin 40 mg daily for 2 weeks
Blood Linoleic Acid Levels	1184.7 nmol Standard Deviation 393.4	1504.7 nmol Standard Deviation 327.8

SECONDARY outcome

Timeframe: 2 weeks

Population: Only participants with complete fasting delta 5 desaturase enzyme activity data were included.

Change in fasting delta 5 desaturase enzyme activity compared to placebo. Delta 5 desaturase enzyme activity is defined as the ratios of C20:4n-6 to C20:3n-6 and C20:5n-3 to C20:4n-3.

Outcome measures

Outcome measures
Measure	Simvastatin 40 mg n=28 Participants Simvastatin 40 mg once daily for 2 weeks followed by placebo once daily for 2 weeks	Placebo n=30 Participants Placebo once daily for 2 weeks followed by simvastatin 40 mg daily for 2 weeks
Change in Fasting Delta 5 Desaturase Enzyme Activity Compared to Placebo Cholesterol ester c20:4n6 / c20:3n6	12.2234 ratio Standard Deviation 3.413	11.5662 ratio Standard Deviation 3.684
Change in Fasting Delta 5 Desaturase Enzyme Activity Compared to Placebo Cholesterol Ester c20:5n3/c20:4n3	17.9161 ratio Standard Deviation 7.738	16.3024 ratio Standard Deviation 9.465

Adverse Events

Simvastatin

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Simvastatin n=30 participants at risk Simvastatin 40 mg tablets once daily for 2 weeks in either Period 1 or Period 2	Placebo n=30 participants at risk Placebo to simvastatin tablets once daily for 2 weeks in either Period 1 or Period 2
Nervous system disorders Tension headache	3.3% 1/30 • Number of events 1	3.3% 1/30 • Number of events 1
Gastrointestinal disorders Diarrhoea	0.00% 0/30	3.3% 1/30 • Number of events 1

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Publications should include input from the investigator(s), and Sponsor personnel. Such input should be reflected in publication authorship. The Sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission. Sponsor review can be expedited to meet publication guidelines.
Publication restrictions are in place

Restriction type: OTHER