Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| TMC114HIV4003 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA | INDUSTRY |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Pravastatin (Pravachol) is approved by the Food and Drug Administration (FDA) and is used to treat high cholesterol. Darunavir (Prezista) and ritonavir (Norvir) are approved by the Food and Drug Administration (FDA) to treat HIV infection. When darunavir and ritonavir are given with pravastatin, they can increase the blood levels of pravastatin. The degree of this interaction varies from person to person. The way that darunavir and ritonavir interact with pravastatin may be affected by a person's genetic make-up. Genetic factors (or DNA) are those that people are born with and that make each person unique. Genetic differences are the reason why one person's body traits such as height and hair color are different from another person's body traits. Genetic differences can also affect the way a medication works in the body or the way two medications interact in the body. The purpose of this clinical study is to determine if a person's genetic make-up affects the way darunavir and ritonavir interact with pravastatin in the body.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| SLCO1B1 Group 1 | Experimental | Participants with the SLCO1B1 *1A/*1A diplotype; Interventions: pravastatin 40 mg by mouth once daily on days 1-4, washout on days 5-11, darunavir 600 mg and ritonavir 100 mg by mouth twice daily on days 12-18, pravastatin 40 mg by mouth once daily on days 15-18. |
|
| SLCO1B1 Group 2 | Experimental | Participants with the SLCO1B1 *1A/*1B or *1B/*1B diplotype; Interventions: Pravastatin 40 mg by mouth once daily on days 1-4, washout on days 5-11, darunavir 600 mg and ritonavir 100 mg by mouth twice daily on days 12-18, pravastatin 40 mg by mouth once daily on days 15-18. |
|
| SLCO1B1 Group 3 | Experimental | Participants who carry at least one SLCO1B1 *5, *15, or *17 diplotype; Interventions: Pravastatin 40 mg by mouth once daily on days 1-4, washout on days 5-11, darunavir 600 mg and ritonavir 100 mg by mouth twice daily on days 12-18, pravastatin 40 mg by mouth once daily on days 15-18. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pravastatin | Drug | Pravastatin 40 mg by mouth daily on days 1-4 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Relative Change in Pravastatin Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval | AUC of pravastatin when administered with darunavir/ritonavir divided by AUC of pravastatin when administered alone. The AUC was measured over a 24-hour dosing interval. | 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose |
| Relative Change in Pravastatin Maximum Plasma Concentration (Cmax) | Cmax of pravastatin when administered with darunavir/ritonavir divided by the Cmax of pravastatin when administered alone. | 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose |
| Measure | Description | Time Frame |
|---|---|---|
| Pravastatin Alone: Pravastatin Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval | Dosing interval of 24 hours | 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose |
| Pravastatin Alone: Pravastatin Maximum Plasma Concentration (Cmax) |
| Measure | Description | Time Frame |
|---|---|---|
| Darunavir Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval | AUC of darunavir over a 12-hour dosing interval. | 0, 1, 2, 3, 4, 5, 6, 8, 12 hours post-dose |
| Darunavir Maximum Plasma Concentration (Cmax) |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Christina L Aquilante, PharmD | University of Colorado, Denver | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Colorado Denver | Aurora | Colorado | 80045 | United States |
Participants were genetically screened for solute carrier organic anion transporter family, member 1B1 (SLCO1B1) diplotypes as follows: Group 1, *1A/*1A (reference diplotype); Group 2, *1A/*1B or *1B/*1B diplotypes; and Group 3, subjects with at least one copy of the *5, *15, or *17 haplotype.
Healthy volunteers were recruited from the Denver metro area between March 2008 and September 2009.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | SLCO1B1 Group 1 | SLCO1B1 *1A/*1A diplotype; Pravastatin 40 mg by mouth daily on days 1-4, washout on days 5-11, darunavir/ritonavir 600/100 mg by mouth twice daily on days 12-18, with pravastatin 40 mg added back on days 15-18 |
| FG001 | SLCO1B1 Group 2 | SLCO1B1 *1A/*1B or *1B/*1B diplotype; Pravastatin 40 mg by mouth daily on days 1-4, washout on days 5-11, darunavir/ritonavir 600/100 mg by mouth twice daily on days 12-18, with pravastatin 40 mg added back on days 15-18. |
| FG002 | SLCO1B1 Group 3 | Carriers of at least one SLCO1B1 *5, *15, or *17 haplotype; Pravastatin 40 mg by mouth daily on days 1-4, washout on days 5-11, darunavir/ritonavir 600/100 mg by mouth twice daily on days 12-18, with pravastatin 40 mg added back on days 15-18 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | SLCO1B1 Group 1 | SLCO1B1 *1A/*1A diplotype; Pravastatin 40 mg by mouth daily on days 1-4, washout on days 5-11, darunavir/ritonavir 600/100 mg by mouth twice daily on days 12-18, with pravastatin 40 mg added back on days 15-18 |
| BG001 | SLCO1B1 Group 2 |
| 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 | Relative Change in Pravastatin Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval | AUC of pravastatin when administered with darunavir/ritonavir divided by AUC of pravastatin when administered alone. The AUC was measured over a 24-hour dosing interval. | The population analyzed included participants who completed the pravastatin alone phase and the pravastatin + darunavir/ritonavir phase of the study. | Posted | Mean | 95% Confidence Interval | ng*hr/ml | 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose |
|
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 | Pravastatin Alone | Pravastatin 40 mg by mouth daily on days 1-4; Includes 32 participants who received at least one dose of pravastatin 40 mg during days 1-4. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Angioedema | General disorders | Systematic Assessment | 1 patient experienced grade 2 angioedema (as described by DAIDS criteria). This was not technically SAE, but did require pharmacologic intervention to prevent a more serious reaction. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | General disorders | Systematic Assessment | Grade 1 per DAIDS criteria. |
The study included only heterozygous carriers of the SLCO1B1 *15 and *17 haplotypes. Pravastatin urine concentrations were not measured; therefore the impact of darunavir/ritonavir on pravastatin renal clearance was not assessed in this population.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Christina Aquilante, Pharm.D. | University of Colorado Denver | 303-724-6126 | christina.aquilante@ucdenver.edu |
Not provided
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| D006949 | Hyperlipidemias |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
Not provided
Not provided
| ID | Term |
|---|---|
| D017035 | Pravastatin |
| D000069454 | Darunavir |
| D019438 | Ritonavir |
| C573645 | WASH protein, Drosophila |
| ID | Term |
|---|---|
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Darunavir | Drug | Darunavir 600mg by mouth twice daily on days 12-18 |
|
|
| Ritonavir | Drug | Ritonavir 100mg by mouth twice daily on days 12-18 |
|
|
| Pravastatin | Drug | Pravastatin 40 mg by mouth daily on days 15-18 |
|
|
| Washout | Other | Washout (no medication) on days 5-11. |
|
| 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose |
| Pravastatin + Darunavir/Ritonavir: Pravastatin Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval | Dosing interval of 24 hours | 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose |
| Pravastatin + Darunavir/Ritonavir: Pravastatin Maximum Plasma Concentration (Cmax) | 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose |
Cmax of darunavir over a 12-hour dosing interval
| 0, 1, 2, 3, 4, 5, 6, 8, 12 hours post-dose |
| Ritonavir Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval | AUC of ritonavir over a 12-hour dosing interval. | 0, 1, 2, 3, 4, 5, 6, 8, 12 hours post-dose |
| Ritonavir Maximum Plasma Concentration (Cmax) | Cmax of ritonavir over a 12-hour dosing interval | 0,1, 2, 3, 4, 5, 6, 8, 12 hours post-dose |
SLCO1B1 *1A/*1B or *1B/*1B diplotype; Pravastatin 40 mg by mouth daily on days 1-4, washout on days 5-11, darunavir/ritonavir 600/100 mg by mouth twice daily on days 12-18, with pravastatin 40 mg added back on days 15-18 |
| BG002 | SLCO1B1 Group 3 | Carriers of at least one SLCO1B1 *5, *15, or *17 haplotype; Pravastatin 40 mg by mouth daily on days 1-4, washout on days 5-11, darunavir/ritonavir 600/100 mg by mouth twice daily on days 12-18, with pravastatin 40 mg added back on days 15-18 |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| SLCO1B1 Group 2 |
SLCO1B1 *1A/*1B or *1B/*1B diplotype; Pravastatin 40 mg by mouth daily on days 1-4, washout on days 5-11, darunavir/ritonavir 600/100 mg by mouth twice daily on days 12-18, with pravastatin 40 mg added back on days 15-18 |
| OG002 | SLCO1B1 Group 3 | Carriers of at least one SLCO1B1 *5, *15, or *17 haplotype; Pravastatin 40 mg by mouth daily on days 1-4, washout on days 5-11, darunavir/ritonavir 600/100 mg by mouth twice daily on days 12-18, with pravastatin 40 mg added back on days 15-18 |
|
|
|
| Primary | Relative Change in Pravastatin Maximum Plasma Concentration (Cmax) | Cmax of pravastatin when administered with darunavir/ritonavir divided by the Cmax of pravastatin when administered alone. | The population analyzed included participants who completed the pravastatin alone phase and the pravastatin + darunavir/ritonavir phase of the study. | Posted | Mean | 95% Confidence Interval | ng/ml | 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose |
|
|
|
|
| Other Pre-specified | Darunavir Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval | AUC of darunavir over a 12-hour dosing interval. | The population analyzed included participants who completed the pravastatin alone phase and the pravastatin + darunavir/ritonavir phase of the study. | Posted | Mean | Standard Deviation | ng*h/ml | 0, 1, 2, 3, 4, 5, 6, 8, 12 hours post-dose |
|
|
|
|
| Other Pre-specified | Darunavir Maximum Plasma Concentration (Cmax) | Cmax of darunavir over a 12-hour dosing interval | The population analyzed included participants who completed the pravastatin alone phase and the pravastatin + darunavir/ritonavir phase of the study. | Posted | Mean | Standard Deviation | ng/ml | 0, 1, 2, 3, 4, 5, 6, 8, 12 hours post-dose |
|
|
|
|
| Other Pre-specified | Ritonavir Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval | AUC of ritonavir over a 12-hour dosing interval. | The population analyzed included participants who completed the pravastatin alone phase and the pravastatin + darunavir/ritonavir phase of the study. | Posted | Mean | Standard Deviation | ng*hr/ml | 0, 1, 2, 3, 4, 5, 6, 8, 12 hours post-dose |
|
|
|
|
| Other Pre-specified | Ritonavir Maximum Plasma Concentration (Cmax) | Cmax of ritonavir over a 12-hour dosing interval | The population analyzed included participants who completed the pravastatin alone phase and the pravastatin + darunavir/ritonavir phase of the study. | Posted | Mean | Standard Deviation | ng/ml | 0,1, 2, 3, 4, 5, 6, 8, 12 hours post-dose |
|
|
|
|
| Secondary | Pravastatin Alone: Pravastatin Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval | Dosing interval of 24 hours | The population analyzed included participants who completed the pravastatin alone phase and the pravastatin + darunavir/ritonavir phase of the study. | Posted | Mean | Standard Deviation | ng*h/ml | 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose |
|
|
|
|
| Secondary | Pravastatin Alone: Pravastatin Maximum Plasma Concentration (Cmax) | The population analyzed included participants who completed the pravastatin alone phase and the pravastatin + darunavir/ritonavir phase of the study. | Posted | Mean | Standard Deviation | ng/ml | 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose |
|
|
|
|
| Secondary | Pravastatin + Darunavir/Ritonavir: Pravastatin Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval | Dosing interval of 24 hours | The population analyzed included participants who completed the pravastatin alone phase and the pravastatin + darunavir/ritonavir phase of the study. | Posted | Mean | Standard Deviation | ng*h/ml | 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose |
|
|
|
|
| Secondary | Pravastatin + Darunavir/Ritonavir: Pravastatin Maximum Plasma Concentration (Cmax) | The population analyzed included participants who completed the pravastatin alone phase and the pravastatin + darunavir/ritonavir phase of the study. | Posted | Mean | Standard Deviation | ng/ml | 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose |
|
|
|
|
| 0 |
| 32 |
| 13 |
| 32 |
| EG001 | Darunavir/Ritonavir Alone | Darunavir/Ritonavir 600/100 mg by mouth twice daily on days 12-14; Includes 31 participants who received at least one dose of darunavir/ritonavir during days 12-14. | 0 | 31 | 22 | 31 |
| EG002 | Pravastatin + Darunavir/Ritonavir | Darunavir/ritonavir 600/100 mg by mouth twice daily and pravastatin 40 mg by mouth once daily on days 15-18. Includes 28 participants who received at least one dose of darunavir/ritonavir and pravastatin during days 15-18. | 1 | 28 | 18 | 28 |
|
| Fatigue | General disorders | Systematic Assessment | Grade 1 per DAIDS criteria. |
|
| Constipation | Gastrointestinal disorders | Systematic Assessment | Grade 1 per DAIDS criteria. |
|
| Muscle pain | Musculoskeletal and connective tissue disorders | Systematic Assessment | Grade 1 per DAIDS criteria. |
|
| Dizziness | General disorders | Systematic Assessment | Grade 1 per DAIDS criteria. |
|
| Hypoalbuminemia | General disorders | Systematic Assessment | Grade 1 per DAIDS criteria. |
|
| Nausea/Vomiting/Dyspepsia/Abdominal Pain | Gastrointestinal disorders | Systematic Assessment | Grade 1 per DAIDS criteria. |
|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment | Grade 1 per DAIDS criteria. |
|
| Anorexia | Gastrointestinal disorders | Systematic Assessment | Grade 1 per DAIDS criteria. |
|
| Shoulder/Neck Pain | Musculoskeletal and connective tissue disorders | Systematic Assessment | Grade 1 per DAIDS criteria. |
|
Prior to publication or presentation, the PI will provide the sponsor with at least 60 days for review of a manuscript
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
| D050171 | Dyslipidemias |
| D052439 | Lipid Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D002219 | Carbamates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D005663 | Furans |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D013844 | Thiazoles |
| D001393 | Azoles |