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The primary objective of this study is to assess the effect of ethinyl estradiol (EE)/norgestimate, a weak cytochrome P450 (CYP) 3A4 inhibitor, on the pharmacokinetics (PK) of lomitapide and 2 primary metabolites, M1 and M3.
This study will be a single center, randomized, open-label, 2 arm study to evaluate the effects of EE/norgestimate, a weak CYP3A4 inhibitor, on the PK of lomitapide in healthy female subjects when EE/norgestimate is administered simultaneously with lomitapide and when administration is separated by 12 hours.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1: Lomitapide & EE/Norgestimate - Taken Together | Experimental | Lomitapide & EE/Norgestimate - Taken Together 2 single oral doses of lomitapide (20 mg) (Day 1 & Day 22) 21 single oral doses of EE/Norgestimate(Day 8 through day 28) |
|
| Arm 2: Lomitapide & EE/Norgestimate - Taken 12 Hours Apart | Experimental | Lomitapide & EE/Norgestimate - Taken 12 hours apart 2 single oral doses of lomitapide (20 mg) (Day 1 & Day 22) 21 single oral doses of EE/Norgestimate(Day 9 through day 29) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| lomitapide | Drug | 20 mg |
|
| Measure | Description | Time Frame |
|---|---|---|
| Cmax for Arm 1 (Lomitapide & EE/Noregestimate - Taken Together) | Maximum observed plasma concentration of lomitapide and its 2 primary metabolites, M1 & M3 | 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing |
| Tmax for Arm 1 (Lomitapide & EE/Noregestimate - Taken Together) | Time to reach maximum observed plasma concentration of lomitapide and its 2 primary metabolites, M1 & M3. | 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing |
| AUC0-t for Arm 1 (Lomitapide & EE/Noregestimate - Taken Together) | Area under the concentration-time curve from zero to last quantifiable concentration of lomitapide and its 2 primary metabolites, M1 & M3. | 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing |
| AUC0-∞ for Arm 1 (Lomitapide & EE/Noregestimate - Taken Together) | Area under the concentration-time curve from zero to infinity of lomitapide and its 2 primary metabolites, M1 & M3. | 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing |
| t1/2 for Arm 1 (Lomitapide & EE/Noregestimate - Taken Together) | Apparent terminal elimination half-life of lomitapide and its 2 primary metabolites, M1 & M3. | 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax for Arm 2 (Lomitapide & EE/Noregestimate - 12 Hours Apart) | Maximum observed plasma concentration of lomitapide and its metabolites, M1 & M3. | 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing |
| Tmax for Arm 2 (Lomitapide & EE/Noregestimate - 12 Hours Apart) |
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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 & EE/Norgestimate - Taken Together | 2 single oral doses of lomitapide (20 mg) (Day 1 & Day 22) 21 single oral doses of EE/Norgestimate(Day 8 through day 28) lomitapide: 20 mg EE/norgestimate: 1x0.035-mg EE/0.25-mg norgestimate tablet |
| FG001 | Lomitapide & EE/Norgestimate - Taken 12 Hours Apart | 2 single oral doses of lomitapide (20 mg) (Day 1 & Day 22) 21 single oral doses of EE/Norgestimate(Day 9 through day 29) lomitapide: 20 mg EE/norgestimate: 1x0.035-mg EE/0.25-mg norgestimate tablet |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Lomitapide & EE/Norgestimate - Taken Together | 2 single oral doses of lomitapide (20 mg) (Day 1 & Day 22) 21 single oral doses of EE/Norgestimate(Day 8 through day 28) lomitapide: 20 mg EE/norgestimate: 1x0.035-mg EE/0.25-mg norgestimate tablet |
| BG001 | Lomitapide & EE/Norgestimate - Taken 12 Hours Apart |
| 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 for Arm 1 (Lomitapide & EE/Noregestimate - Taken Together) | Maximum observed plasma concentration of lomitapide and its 2 primary metabolites, M1 & M3 | The Pharmacokinetic Analysis population included all subjects. Only subjects who completed both periods were included in the ANOVA analyses. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 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 & EE/Norgestimate - Taken Together | 2 single oral doses of lomitapide (20 mg) (Day 1 & Day 22) 21 single oral doses of EE/Norgestimate(Day 8 through day 28) lomitapide: 20 mg EE/norgestimate: 1x0.035-mg EE/0.25-mg norgestimate tablet |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Alison Long, MD - VP Clinical | Aegerion Pharmaceuticals, Inc. | 617-500-5142 | alison.long@aegerion.com |
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| ID | Term |
|---|---|
| C473731 | BMS201038 |
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| EE/norgestimate | Drug | 1x0.035-mg EE/0.25-mg norgestimate tablet |
|
|
Time to reach maximum observed plasma concentration of lomitapide and its metabolites, M1 & M3. |
| 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing |
| AUC0-t for Arm 2 (Lomitapide & EE/Noregestimate - 12 Hours Apart) | Area under the concentration-time curve from zero to last quantifiable concentration of lomitapide and its metabolites, M1 & M3. | 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing |
| AUC0-∞ for Arm 2 (Lomitapide & EE/Noregestimate - 12 Hours Apart) | Area under the concentration-time curve from zero to infinity of lomitapide and its metabolites, M1 & M3. | 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing |
| t1/2 for Arm 2 (Lomitapide & EE/Noregestimate - 12 Hours Apart) | Apparent terminal elimination half-life of lomitapide and its metabolites, M1 & M3. | 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing |
2 single oral doses of lomitapide (20 mg) (Day 1 & Day 22) 21 single oral doses of EE/Norgestimate(Day 9 through day 29) lomitapide: 20 mg EE/norgestimate: 1x0.035-mg EE/0.25-mg norgestimate tablet |
| 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 |
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| 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 EE/Norgestimate 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 EE/Norgestimate simultaneously |
|
|
| Primary | Tmax for Arm 1 (Lomitapide & EE/Noregestimate - Taken Together) | Time to reach maximum observed plasma concentration of lomitapide and its 2 primary metabolites, M1 & M3. | The Pharmacokinetic Analysis population included all subjects. Only subjects who completed both periods were included in the ANOVA analyses. | Posted | Median | Full Range | hr | 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing |
|
|
|
| Primary | AUC0-t for Arm 1 (Lomitapide & EE/Noregestimate - Taken Together) | Area under the concentration-time curve from zero to last quantifiable concentration of lomitapide and its 2 primary metabolites, M1 & M3. | The Pharmacokinetic Analysis population included all subjects. Only subjects who completed both periods were included in the ANOVA analyses. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing |
|
|
|
| Primary | AUC0-∞ for Arm 1 (Lomitapide & EE/Noregestimate - Taken Together) | Area under the concentration-time curve from zero to infinity of lomitapide and its 2 primary metabolites, M1 & M3. | The Pharmacokinetic Analysis population included all subjects. Only subjects who completed both periods were included in the ANOVA analyses. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing |
|
|
|
| Primary | t1/2 for Arm 1 (Lomitapide & EE/Noregestimate - Taken Together) | Apparent terminal elimination half-life of lomitapide and its 2 primary metabolites, M1 & M3. | The Pharmacokinetic Analysis population included all subjects. Only subjects who completed both periods were included in the ANOVA analyses. | Posted | Geometric Mean | Geometric Coefficient of Variation | hr | 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing |
|
|
|
| Secondary | Cmax for Arm 2 (Lomitapide & EE/Noregestimate - 12 Hours Apart) | Maximum observed plasma concentration of lomitapide and its metabolites, M1 & M3. | The Pharmacokinetic Analysis population included all subjects. Only subjects who completed both periods were included in the ANOVA analyses. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing |
|
|
|
| Secondary | Tmax for Arm 2 (Lomitapide & EE/Noregestimate - 12 Hours Apart) | Time to reach maximum observed plasma concentration of lomitapide and its metabolites, M1 & M3. | The Pharmacokinetic Analysis population included all subjects. Only subjects who completed both periods were included in the ANOVA analyses. | Posted | Mean | Full Range | hr | 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing |
|
|
|
| Secondary | AUC0-t for Arm 2 (Lomitapide & EE/Noregestimate - 12 Hours Apart) | Area under the concentration-time curve from zero to last quantifiable concentration of lomitapide and its metabolites, M1 & M3. | The Pharmacokinetic Analysis population included all subjects. Only subjects who completed both periods were included in the ANOVA analyses. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing |
|
|
|
| Secondary | AUC0-∞ for Arm 2 (Lomitapide & EE/Noregestimate - 12 Hours Apart) | Area under the concentration-time curve from zero to infinity of lomitapide and its metabolites, M1 & M3. | The Pharmacokinetic Analysis population included all subjects. Only subjects who completed both periods were included in the ANOVA analyses. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing |
|
|
|
| Secondary | t1/2 for Arm 2 (Lomitapide & EE/Noregestimate - 12 Hours Apart) | Apparent terminal elimination half-life of lomitapide and its metabolites, M1 & M3. | The Pharmacokinetic Analysis population included all subjects. Only subjects who completed both periods were included in the ANOVA analyses. | Posted | Geometric Mean | Geometric Coefficient of Variation | hr | 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 169 hours after dosing |
|
|
|
| 0 |
| 16 |
| 0 |
| 16 |
| 8 |
| 16 |
| EG001 | Lomitapide & EE/Norgestimate - Taken 12 Hours Apart | 2 single oral doses of lomitapide (20 mg) (Day 1 & Day 22) 21 single oral doses of EE/Norgestimate(Day 9 through day 29) lomitapide: 20 mg EE/norgestimate: 1x0.035-mg EE/0.25-mg norgestimate tablet | 0 | 16 | 0 | 16 | 7 | 16 |
| Vomitting | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
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| Procedural dizziness | Injury, poisoning and procedural complications | MedDRA (16.1) | Systematic Assessment |
|
| Procedural Nausea | Injury, poisoning and procedural complications | MedDRA (16.1) | Systematic Assessment |
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| Laceration | Injury, poisoning and procedural complications | MedDRA (16.1) | Systematic Assessment |
|
| Vessel Punction Site Pain | General disorders | MedDRA (16.1) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (16.1) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
|
| Presyncope | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
|
| Sensory disturbance | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (16.1) | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (16.1) | Systematic Assessment |
|
| Pulmonary congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (16.1) | Systematic Assessment |
|
| Rhinorrhea | Respiratory, thoracic and mediastinal disorders | MedDRA (16.1) | Systematic Assessment |
|
| Sneezing | Respiratory, thoracic and mediastinal disorders | MedDRA (16.1) | Systematic Assessment |
|
| Dysmenorrhoea | Reproductive system and breast disorders | MedDRA (16.1) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (16.1) | Systematic Assessment |
|
| hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA (16.1) | Systematic Assessment |
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| Fungal infection | Infections and infestations | MedDRA (16.1) | Systematic Assessment |
|
| Body temperature increased | Investigations | MedDRA (16.1) | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (16.1) | Systematic Assessment |
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| Dysuria | Renal and urinary disorders | MedDRA (16.1) | Systematic Assessment |
|
| Hot flush | Vascular disorders | MedDRA (16.1) | Systematic Assessment |
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Described in site contract