Not provided
Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2009_609 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The purpose of this study was to provide human lipidomics standards with simvastatin treatment that were to be used for comparison with similar preclinical studies.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Simvastatin 40 mg first, then placebo | Experimental | Simvastatin 40 mg tablets once daily for 2 weeks followed by placebo for 2 weeks |
|
| Placebo first, then simvastatin 40 mg once daily | Placebo Comparator | Placebo for 2 weeks followed by simvastatin 40 mg once daily for 2 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Simvastatin | Drug | 40 mg once daily for 2 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Arachidonic Acid Level After 2 Weeks of Treatment | 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. | 2 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Fasting Blood Lipidomic Levels After 2 Weeks of Treatment | Change in fasting blood cholesterol ester, lysophosphatidylcholine, phosphatidylcholine, phosphatidylethanolamine, and triacylglycerol levels compared to placebo. The mean reported was an adjusted mean. | 2 weeks |
| Serum Proprotein Convertase Subtilisin-like/Kexin Type 9 (PCSK9) Level |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21417623 | Derived | Chen F, Maridakis V, O'Neill EA, Hubbard BK, Strack A, Beals C, Herman GA, Wong P. The effects of simvastatin treatment on plasma lipid-related biomarkers in men with dyslipidaemia. Biomarkers. 2011 Jun;16(4):321-33. doi: 10.3109/1354750X.2011.561367. Epub 2011 Mar 21. |
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Simvastatin 40 mg, Then Placebo | Simvastatin 40 mg once daily for 2 weeks followed by placebo once daily for 2 weeks |
| FG001 | Placebo First, Then Simvastatin 40 mg | Placebo once daily for 2 weeks followed by simvastatin 40 mg daily for 2 weeks |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 |
|
| ||||||||||||||||||
| Period 2 |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | All Participants | All enrolled participants |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Arachidonic Acid Level After 2 Weeks of Treatment | 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. | Only participants with complete arachidonic acid data were included. | Posted | Mean | Standard Deviation | nmol | 2 weeks |
|
Not provided
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Simvastatin | Simvastatin 40 mg tablets once daily for 2 weeks in either Period 1 or Period 2 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Tension headache | Nervous system disorders | MedDRA 12.1 | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D006937 | Hypercholesterolemia |
| D050171 | Dyslipidemias |
| ID | Term |
|---|---|
| D006949 | Hyperlipidemias |
| D052439 | Lipid Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D019821 | Simvastatin |
| ID | Term |
|---|---|
| D008148 | Lovastatin |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Placebo | Drug | Placebo, matching the simvastatin (40 mg) tablet as a single oral daily dose for 2 weeks |
|
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). |
| 2 weeks |
| Blood Linoleic Acid Levels | Change in blood linoleic acid levels for Cholesterol Ester compared to placebo. | 2 weeks |
| Change in Fasting Delta 5 Desaturase Enzyme Activity Compared to Placebo | 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. | 2 weeks |
| NOT COMPLETED |
|
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
|
|
|
| Secondary | Fasting Blood Lipidomic Levels After 2 Weeks of Treatment | Change in fasting blood cholesterol ester, lysophosphatidylcholine, phosphatidylcholine, phosphatidylethanolamine, and triacylglycerol levels compared to placebo. The mean reported was an adjusted mean. | 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. | Posted | Mean | Standard Deviation | nmol | 2 weeks |
|
|
|
|
| Secondary | Serum Proprotein Convertase Subtilisin-like/Kexin Type 9 (PCSK9) Level | 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). | Only participants with complete PCSK9 data were included. | Posted | Mean | Standard Deviation | nmol | 2 weeks |
|
|
|
|
| Secondary | Blood Linoleic Acid Levels | Change in blood linoleic acid levels for Cholesterol Ester compared to placebo. | Only participants with complete blood linoleic acid data were included. | Posted | Mean | Standard Deviation | nmol | 2 weeks |
|
|
|
| Secondary | Change in Fasting Delta 5 Desaturase Enzyme Activity Compared to Placebo | 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. | Only participants with complete fasting delta 5 desaturase enzyme activity data were included. | Posted | Mean | Standard Deviation | ratio | 2 weeks |
|
|
|
|
| 0 |
| 30 |
| 1 |
| 30 |
| EG001 | Placebo | Placebo to simvastatin tablets once daily for 2 weeks in either Period 1 or Period 2 | 0 | 30 | 2 | 30 |
| Diarrhoea | Gastrointestinal disorders | MedDRA 12.1 | Systematic Assessment |
|
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.
| D006844 |
| Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| Cholesterol ester lipid 20:3n6 |
|
| Cholesterol ester lipid 20:3n9 |
|
| Cholesterol ester lipid 22:5n6 |
|
| Cholesterol ester lipid 22:6n3 |
|
| Lysophosphatidyl-choline lipid 20:4n6 |
|
| Phosphatidyl-choline lipid 18:2n6 |
|
| Phosphatidyl-choline lipid 20:3n6 |
|
| Phosphatidyl-choline lipid 20:4n6 |
|
| Phosphatidyl-choline lipid 22:5n3 |
|
| Phosphatidyl-choline lipid 22:5n6 |
|
| Phosphatidyl-ethanolamine lipid 18:2n6 |
|
| Triacylglycerol 16:00 |
|
| Triacylglycerol 20:3n9 |
|
|
Cholesterol Ester 18:3n3 |
| Mixed Models Analysis |
An unstructured covariance and Kenward Roger degrees of freedom were assumed. |
| <0.001 |
Endpoint was analyzed as appropriate for a 2-period crossover model using a mixed model with fixed terms of period and treatment with participants as a random factor. |
| Mean Difference (Final Values) |
| -4.5 |
| 95 |
| No |
| Superiority or Other |
| Cholesterol Ester 20:3n6 | Mixed Models Analysis | An unstructured covariance and Kenward Roger degrees of freedom were assumed. | 0.217 | Endpoint was analyzed as appropriate for a 2-period crossover model using a mixed model with fixed terms of period and treatment with participants as a random factor. | Mean Difference (Final Values) | -2.5 | 95 | No | Superiority or Other |
| Cholesterol Ester 20:3n9 | Mixed Models Analysis | An unstructured covariance and Kenward Roger degrees of freedom were assumed. | 0.666 | Endpoint was analyzed as appropriate for a 2-period crossover model using a mixed model with fixed terms of period and treatment with participants as a random factor. | Mean Difference (Final Values) | 0.1 | 95 | No | Superiority or Other |
| Cholesterol Ester 22:5n6 | Mixed Models Analysis | An unstructured covariance and Kenward Roger degrees of freedom were assumed. | 0.776 | Endpoint was analyzed as appropriate for a 2-period crossover model using a mixed model with fixed terms of period and treatment with participants as a random factor. | Mean Difference (Final Values) | 0.0 | 95 | No | Superiority or Other |
| Cholesterol Ester 22:6n3 | Mixed Models Analysis | An unstructured covariance and Kenward Roger degrees of freedom were assumed. | 0.018 | Endpoint was analyzed as appropriate for a 2-period crossover model using a mixed model with fixed terms of period and treatment with participants as a random factor. | Mean Difference (Final Values) | -2.5 | 95 | No | Superiority or Other |
| Lysophosphatidylcholine 20:4n6 | Mixed Models Analysis | An unstructured covariance and Kenward Roger degrees of freedom were assumed. | 0.152 | Endpoint was analyzed as appropriate for a 2-period crossover model using a mixed model with fixed terms of period and treatment with participants as a random factor. | Mean Difference (Final Values) | 1.1 | 95 | No | Superiority or Other |
| Phosphatidylcholine 18:2n6 | Mixed Models Analysis | An unstructured covariance and Kenward Roger degrees of freedom were assumed. | 0.007 | Endpoint was analyzed as appropriate for a 2-period crossover model using a mixed model with fixed terms of period and treatment with participants as a random factor. | Mean Difference (Final Values) | -132.1 | 95 | No | Superiority or Other |
| Phosphatidylcholine 20:3n6 | Mixed Models Analysis | An unstructured covariance and Kenward Roger degrees of freedom were assumed. | 0.325 | Endpoint was analyzed as appropriate for a 2-period crossover model using a mixed model with fixed terms of period and treatment with participants as a random factor. | Mean Difference (Final Values) | -11.8 | 95 | No | Superiority or Other |
| Phosphatidylcholine 20:4n6 | Mixed Models Analysis | An unstructured covariance and Kenward Roger degrees of freedom were assumed. | 0.419 | Endpoint was analyzed as appropriate for a 2-period crossover model using a mixed model with fixed terms of period and treatment with participants as a random factor. | Mean Difference (Final Values) | 18.3 | 95 | No | Superiority or Other |
| Phosphatidylcholine 22:5n3 | Mixed Models Analysis | An unstructured covariance and Kenward Roger degrees of freedom were assumed. | 0.070 | Endpoint was analyzed as appropriate for a 2-period crossover model using a mixed model with fixed terms of period and treatment with participants as a random factor. | Mean Difference (Final Values) | -4.7 | 95 | No | Superiority or Other |
| Phosphatidylcholine 22:5n6 | Mixed Models Analysis | An unstructured covariance and Kenward Roger degrees of freedom were assumed. | 0.769 | Endpoint was analyzed as appropriate for a 2-period crossover model using a mixed model with fixed terms of period and treatment with participants as a random factor. | Mean Difference (Final Values) | -0.2 | 95 | No | Superiority or Other |
| Phosphatidylethanolamine 18:2n6 | Mixed Models Analysis | An unstructured covariance and Kenward Roger degrees of freedom were assumed. | <0.001 | Endpoint was analyzed as appropriate for a 2-period crossover model using a mixed model with fixed terms of period and treatment with participants as a random factor. | Mean Difference (Final Values) | -11.1 | 95 | No | Superiority or Other |
| Triacylglycerol 16:00 | Mixed Models Analysis | An unstructured covariance and Kenward Roger degrees of freedom were assumed. | 0.016 | Endpoint was analyzed as appropriate for a 2-period crossover model using a mixed model with fixed terms of period and treatment with participants as a random factor. | Mean Difference (Final Values) | -240.8 | 95 | No | Superiority or Other |
| Triacylglycerol 20:3n9 | Mixed Models Analysis | An unstructured covariance and Kenward Roger degrees of freedom were assumed. | 0.833 | Endpoint was analyzed as appropriate for a 2-period crossover model using a mixed model with fixed terms of period and treatment with participants as a random factor. | Mean Difference (Final Values) | 0.1 | 95 | No | Superiority or Other |
|
Fed |
| Mixed Models Analysis |
An unstructured covariance and Kenward Roger degrees of freedom were assumed. |
| <0.001 |
Endpoint was analyzed as appropriate for a 2-period crossover model using a mixed model with fixed terms of period and treatment with participants as a random factor. |
| Mean Difference (Final Values) |
| 1.40 |
| 95 |
| No |
| Superiority or Other |
| 0.151 |
| 95 |
| No |
| Superiority or Other |