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The primary objective of this study is to assess the effect of atorvastatin, a weak cytochrome P450 (CYP) 3A4 inhibitor, on the pharmacokinetics (PK) of lomitapide and its 2 primary metabolites, M1 and M3.
This study will be a single center, randomized, open-label, 2-arm study to evaluate the effects of atorvastatin, a weak CYP3A4 inhibitor, on the PK of lomitapide in healthy male and female subjects when atorvastatin is administered simultaneously with lomitapide and when it is administered 12 hours after lomitapide.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Lomitapide & Atorvastatin - Taken Together | Experimental | 2 single oral doses of lomitapide (20 mg) with a 14-day washout between (Day 1 & Day 15) 11 single oral doses of atorvastatin (80 mg) (Day 11 through day 21) |
|
| Lomitapide & Atorvastatin - Approx. 12 hours between | Experimental | 2 single oral doses of lomitapide (20 mg) with a 14-day washout between (Day 1 & Day 15) 11 single oral doses of atorvastatin (80 mg) (Day 12 through day 22) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| lomitapide | Drug | 20 mg dose |
|
| Measure | Description | Time Frame |
|---|---|---|
| Cmax | Maximum observed plasma concentration of lomitapide and its 2 primary metabolites (M1 & M3), following administration of lomitapide alone and coadministered with atorvastatin simultaneously (Arm 1) | Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing |
| Tmax | Time to reach maximum observed plasma concentration of lomitapide and its 2 primary metabolites (M1 & M3), following administration of lomitapide alone and coadministered with atorvastatin simultaneously (Arm 1) | Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing |
| AUC0-t | Area under the concentration-time curve from zero to the last quantifiable concentration of lomitapide and its 2 primary metabolites (M1 & M3), following administration of lomitapide alone and coadministered with atorvastatin simultaneously (Arm 1) | Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing |
| AUC0-∞ | Area under the concentration-time curve from zero to infinity of lomitapide and its 2 primary metabolites (M1 & M3), following administration of lomitapide alone and coadministered with atorvastatin simultaneously (Arm 1) | Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing |
| t1/2 | Apparent terminal elimination half-life of lomitapide and its 2 primary metabolites (M1 & M3), following administration of lomitapide alone and coadministered with atorvastatin simultaneously (Arm 1) | Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax | Maximum observed plasma concentration of lomitapide and its 2 primary metabolites (M1 & M3) following administration of lomitapide alone and coadministered with atorvastatin 12 hours apart (Arm 2) | Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Mark Sumeray, MD | Cheif Medical Officer | Study Chair |
| T. Alex King, MD, CPI | Covance | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Covance Clinical Research Unit, Inc | Dallas | Texas | 75247 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Lomitapide & Atorvastatin - Taken Together | 2 single oral doses of lomitapide (20 mg) with a 14-day washout between (Day 1 & Day 15) 11 single oral doses of atorvastatin (80 mg) (Day 11 through day 21) lomitapide: 20 mg dose Atorvastatin: 80 mg |
| FG001 | Lomitapide & Atorvastatin - Approx. 12 Hours Between | 2 single oral doses of lomitapide (20 mg) with a 14-day washout between (Day 1 & Day 15) 11 single oral doses of atorvastatin (80 mg) (Day 12 through day 22) lomitapide: 20 mg dose Atorvastatin: 80 mg |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Lomitapide & Atorvastatin - Taken Together | 2 single oral doses of lomitapide (20 mg) with a 14-day washout between (Day 1 & Day 15) 11 single oral doses of atorvastatin (80 mg) (Day 11 through day 21) lomitapide: 20 mg dose Atorvastatin: 80 mg |
| BG001 | Lomitapide & Atorvastatin - Approx. 12 Hours Between |
| 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 | Cmax | Maximum observed plasma concentration of lomitapide and its 2 primary metabolites (M1 & M3), following administration of lomitapide alone and coadministered with atorvastatin simultaneously (Arm 1) | The PK Population consisted of all subjects who received at least one dose of study drug and have evaluable PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Lomitapide & Atorvastatin - Taken Together | 2 single oral doses of lomitapide (20 mg) with a 14-day washout between (Day 1 & Day 15) 11 single oral doses of atorvastatin (80 mg) (Day 11 through day 21) lomitapide: 20 mg dose Atorvastatin: 80 mg |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA 16.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Alison Long, MD - VP Clinical | Aegerion Pharmaceuticals, Inc. | 617-242-5142 | alison.long@aegerion.com |
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| ID | Term |
|---|---|
| C473731 | BMS201038 |
| D000069059 | Atorvastatin |
| ID | Term |
|---|---|
| D011758 | Pyrroles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Atorvastatin | Drug | 80 mg |
|
|
| Tmax |
Time to reach maximum observed plasma concentration of lomitapide and its 2 primary metabolites (M1 & M3) following administration of lomitapide alone and coadministered with atorvastatin 12 hours apart (Arm 2) |
| Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing |
| AUC0-t | Area under the concentration-time curve from zero to the last quantifiable concentration of lomitapide and its 2 primary metabolites (M1 & M3) following administration of lomitapide alone and coadministered with atorvastatin 12 hours apart (Arm 2) | Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing |
| AUC0-∞ | Area under the concentration-time curve from zero to infinity of lomitapide and its 2 primary metabolites (M1 & M3) following administration of lomitapide alone and coadministered with atorvastatin 12 hours apart (Arm 2) | Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing |
| t1/2 | Apparent terminal elimination half-life of lomitapide and its 2 primary metabolites (M1 & M3) following administration of lomitapide alone and coadministered with atorvastatin 12 hours apart (Arm 2) | Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing |
2 single oral doses of lomitapide (20 mg) with a 14-day washout between (Day 1 & Day 15) 11 single oral doses of atorvastatin (80 mg) (Day 12 through day 22) lomitapide: 20 mg dose Atorvastatin: 80 mg |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
PK of lomitapide following administration of lomitapide coadministered with atorvastatin simultaneously
| OG002 | PK of M1 (Lomitapide Alone) | PK of M1 following administration of lomitapide alone |
| OG003 | PK of M1 (Coadministered Simultaneously) | PK of M1 following administration of lomitapide coadministered with atorvastatin simultaneously |
| OG004 | PK of M3 (Lomitapide Alone) | PK of M3 following administration of lomitapide alone |
| OG005 | PK of M3 (Coadministered Simultaneously) | PK of M3 following administration of lomitapide coadministered with atorvastatin simultaneously |
|
|
| Primary | Tmax | Time to reach maximum observed plasma concentration of lomitapide and its 2 primary metabolites (M1 & M3), following administration of lomitapide alone and coadministered with atorvastatin simultaneously (Arm 1) | The PK Population consisted of all subjects who received at least one dose of study drug and had evaluable PK data. | Posted | Median | Full Range | hr | Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing |
|
|
|
| Primary | AUC0-t | Area under the concentration-time curve from zero to the last quantifiable concentration of lomitapide and its 2 primary metabolites (M1 & M3), following administration of lomitapide alone and coadministered with atorvastatin simultaneously (Arm 1) | The PK Population consisted of all subjects who received at least one dose of study drug and had evaluable PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing |
|
|
|
| Secondary | Cmax | Maximum observed plasma concentration of lomitapide and its 2 primary metabolites (M1 & M3) following administration of lomitapide alone and coadministered with atorvastatin 12 hours apart (Arm 2) | The PK Population consisted of all subjects who received at least one dose of study drug and have evaluable PK data. 1 subject was removed from formal statistical analysis due to all BLQ values on Day 1 for lomitapide, M1 and M3. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing |
|
|
|
| Primary | AUC0-∞ | Area under the concentration-time curve from zero to infinity of lomitapide and its 2 primary metabolites (M1 & M3), following administration of lomitapide alone and coadministered with atorvastatin simultaneously (Arm 1) | The PK Population consisted of all subjects who received at least one dose of study drug and had evaluable PK data. 2 subjects were removed from formal statistical analysis of "PK of M3 (Lomitapide alone)" due to missing value of AUC0-∞ for Analyte M3. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing |
|
|
|
| Primary | t1/2 | Apparent terminal elimination half-life of lomitapide and its 2 primary metabolites (M1 & M3), following administration of lomitapide alone and coadministered with atorvastatin simultaneously (Arm 1) | The PK Population consisted of all subjects who received at least one dose of study drug and have evaluable PK data. 2 subjects were removed from formal statistical analysis of "PK of M3 (Lomitapide alone)" due to missing value of AUC0-∞ for Analyte M3. | Posted | Geometric Mean | Geometric Coefficient of Variation | hr | Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing |
|
|
|
| Secondary | Tmax | Time to reach maximum observed plasma concentration of lomitapide and its 2 primary metabolites (M1 & M3) following administration of lomitapide alone and coadministered with atorvastatin 12 hours apart (Arm 2) | The PK Population consisted of all subjects who received at least one dose of study drug and have evaluable PK data. 1 subject was removed from formal statistical analysis due to all BLQ values on Day 1 for lomitapide, M1 and M3. | Posted | Median | Full Range | hr | Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing |
|
|
|
| Secondary | AUC0-t | Area under the concentration-time curve from zero to the last quantifiable concentration of lomitapide and its 2 primary metabolites (M1 & M3) following administration of lomitapide alone and coadministered with atorvastatin 12 hours apart (Arm 2) | The PK Population consisted of all subjects who received at least one dose of study drug and have evaluable PK data. 1 subject was removed from formal statistical analysis due to all BLQ values on Day 1 for lomitapide, M1 and M3. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing |
|
|
|
| Secondary | AUC0-∞ | Area under the concentration-time curve from zero to infinity of lomitapide and its 2 primary metabolites (M1 & M3) following administration of lomitapide alone and coadministered with atorvastatin 12 hours apart (Arm 2) | The PK Population consisted of all subjects who received at least one dose of study drug and have evaluable PK data. 3 subjects were removed from formal statistical analysis due to BLQ values on Day 1, missing value of AUC0-∞ on Day 1, and missing value of AUC0-∞ on Day 15. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing |
|
|
|
| Secondary | t1/2 | Apparent terminal elimination half-life of lomitapide and its 2 primary metabolites (M1 & M3) following administration of lomitapide alone and coadministered with atorvastatin 12 hours apart (Arm 2) | The PK Population consisted of all subjects who received at least one dose of study drug and have evaluable PK data. 3 subjects were removed from formal statistical analysis due to BLQ values on Day 1, missing value of AUC0-∞ on Day 1, and missing value of AUC0-∞ on Day 15. | Posted | Geometric Mean | Geometric Coefficient of Variation | hr | Predose and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours after dosing |
|
|
|
| 0 |
| 16 |
| 0 |
| 16 |
| 12 |
| 16 |
| EG001 | Lomitapide & Atorvastatin - Approx. 12 Hours Between | 2 single oral doses of lomitapide (20 mg) with a 14-day washout between (Day 1 & Day 15) 11 single oral doses of atorvastatin (80 mg) (Day 12 through day 22) lomitapide: 20 mg dose Atorvastatin: 80 mg | 0 | 16 | 0 | 16 | 5 | 16 |
| Abdominal Pain | Gastrointestinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Blister | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Systematic Assessment |
|
| Dry Skin | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Systematic Assessment |
|
| Skin Irritation | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Systematic Assessment |
|
| Decreased Appitite | Metabolism and nutrition disorders | MedDRA 16.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 16.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 16.1 | Systematic Assessment |
|
| Neck Pain | Musculoskeletal and connective tissue disorders | MedDRA 16.1 | Systematic Assessment |
|
| Dysmenorrhoea | Reproductive system and breast disorders | MedDRA 16.1 | Systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA 16.1 | Systematic Assessment |
|
| Lip Dry | Gastrointestinal disorders | MedDRA 16.1 | Systematic Assessment |
|
Described in site contract.
| D006538 |
| Heptanoic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |