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| ID | Type | Description | Link |
|---|---|---|---|
| 152252 | Other Grant/Funding Number | ViiV Healthcare |
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The investigator believes simeprevir concentrations are unchanged when administered in combination with dolutegravir relative to administration alone. The investigator believes dolutegravir concentrations are unchanged when administered in combination with simeprevir. Additionally, the investigator believes simeprevir and dolutegravir are safe when administered alone and in combination.
To investigate the potential for drug interactions between simeprevir and dolutegravir, participants will receive each drug alone and the drugs in combination for 7 days. The pharmacokinetics of simeprevir and dolutegravir when given in combination vs. alone will be compared.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sequence 1a | Experimental | Sequence 1,2,3: simeprevir only, then dolutegravir only, then both simeprevir and dolutegravir. |
|
| Sequence 1b | Experimental | Sequence 1,3,2: simeprevir only, then both simeprevir and dolutegravir, then dolutegravir only. |
|
| Sequence 2a | Experimental | Sequence 2,1,3: dolutegravir only, then simeprevir only, then both simeprevir and dolutegravir. |
|
| Sequence 2b | Experimental | Sequence 2,3,1: dolutegravir only, then both simeprevir and dolutegravir, then simeprevir only. |
|
| Sequence 3a | Experimental | Sequence 3,1,2: both simeprevir and dolutegravir, then simeprevir only, then dolutegravir only. |
|
| Sequence 3b |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| dolutegravir | Drug | dolutegravir tablets 50mg, once daily x 7 days. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Simeprevir AUC Pharmacokinetics | Determine simeprevir area-under-the concentration time curve (AUC) when administered alone and when being co-administered with Dolutegravier. | Pre-dose and, 1, 2, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose on day 7 |
| Dolutegravir AUC Pharmacokinetics | Determine Dolutegravir area-under-the concentration time curve (AUC) when administered alone and when co-administered with simeprevir. | Pre-dose and, 1, 2, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose on day 7 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jennifer J Kiser, PharmD | University of Colorado, Denver | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Colorado Anschutz Medical Campus | Aurora | Colorado | 80045 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29029135 | Derived | MacBrayne CE, Castillo-Mancilla J, Burton JR Jr, MaWhinney S, Wagner CB, Micke K, Fey J, Huntley RT, Larson B, Bushman LR, Kiser JJ. Small increase in dolutegravir trough, but equivalent total dolutegravir exposure with simeprevir in HIV/HCV seronegative volunteers. J Antimicrob Chemother. 2018 Jan 1;73(1):156-159. doi: 10.1093/jac/dkx344. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Sequence 1a | Sequence 1,2,3: simeprevir only, then dolutegravir only, then both simeprevir and dolutegravir. dolutegravir: dolutegravir tablets 50mg, once daily x 7 days. simeprevir: simeprevir tablets 150mg, once daily x 7 days. |
| FG001 | Sequence 1b | Sequence 1,3,2: simeprevir only, then both simeprevir and dolutegravir, then dolutegravir only. dolutegravir: dolutegravir tablets 50mg, once daily x 7 days. simeprevir: simeprevir tablets 150mg, once daily x 7 days. |
| FG002 | Sequence 2a | Sequence 2,1,3: dolutegravir only, then simeprevir only, then both simeprevir and dolutegravir. dolutegravir: dolutegravir tablets 50mg, once daily x 7 days. simeprevir: simeprevir tablets 150mg, once daily x 7 days. |
| FG003 | Sequence 2b | Sequence 2,3,1: dolutegravir only, then both simeprevir and dolutegravir, then simeprevir only. dolutegravir: dolutegravir tablets 50mg, once daily x 7 days. simeprevir: simeprevir tablets 150mg, once daily x 7 days. |
| FG004 | Sequence 3a | Sequence 3,1,2: both simeprevir and dolutegravir, then simeprevir only, then dolutegravir only. dolutegravir: dolutegravir tablets 50mg, once daily x 7 days. simeprevir: simeprevir tablets 150mg, once daily x 7 days. |
| FG005 | Sequence 3b | Sequence 3,2,1: Both simeprevir and dolutegravir, then dolutegravir only, then simeprevir only. dolutegravir: dolutegravir tablets 50mg, once daily x 7 days. simeprevir: simeprevir tablets 150mg, once daily x 7 days. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Sequence 1a | Sequence 1,2,3: simeprevir only, then dolutegravir only, then both simeprevir and dolutegravir. dolutegravir: dolutegravir tablets 50mg, once daily x 7 days. simeprevir: simeprevir tablets 150mg, once daily x 7 days. |
| BG001 | Sequence 1b |
| 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 | Simeprevir AUC Pharmacokinetics | Determine simeprevir area-under-the concentration time curve (AUC) when administered alone and when being co-administered with Dolutegravier. | Only arms that included Simeprevir administration are included. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | Pre-dose and, 1, 2, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose on day 7 |
|
Time of consenting to study exit (Phone follow up 7 days after final intensive PK visit, max 3 months)
AEs were graded per the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0, November, 2014. Available: http://rsc.tech-res.com/safetyandpharmacovigilance/.
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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 | Simeprevir Only | Simeprevir tablets 150mg, once daily x 7 days. | 0 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Jennifer Kiser | University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences | (303) 724-6131 | jennifer.kiser@ucdenver.edu |
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| ID | Term |
|---|---|
| D006526 | Hepatitis C |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D006525 | Hepatitis, Viral, Human |
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| ID | Term |
|---|---|
| C562325 | dolutegravir |
| D000069616 | Simeprevir |
| ID | Term |
|---|---|
| D013449 | Sulfonamides |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
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| Experimental |
Sequence 3,2,1: Both simeprevir and dolutegravir, then dolutegravir only, then simeprevir only. |
|
| simeprevir | Drug | simeprevir tablets 150mg, once daily x 7 days. |
|
Sequence 1,3,2: simeprevir only, then both simeprevir and dolutegravir, then dolutegravir only. dolutegravir: dolutegravir tablets 50mg, once daily x 7 days. simeprevir: simeprevir tablets 150mg, once daily x 7 days. |
| BG002 | Sequence 2a | Sequence 2,1,3: dolutegravir only, then simeprevir only, then both simeprevir and dolutegravir. dolutegravir: dolutegravir tablets 50mg, once daily x 7 days. simeprevir: simeprevir tablets 150mg, once daily x 7 days. |
| BG003 | Sequence 2b | Sequence 2,3,1: dolutegravir only, then both simeprevir and dolutegravir, then simeprevir only. dolutegravir: dolutegravir tablets 50mg, once daily x 7 days. simeprevir: simeprevir tablets 150mg, once daily x 7 days. |
| BG004 | Sequence 3a | Sequence 3,1,2: both simeprevir and dolutegravir, then simeprevir only, then dolutegravir only. dolutegravir: dolutegravir tablets 50mg, once daily x 7 days. simeprevir: simeprevir tablets 150mg, once daily x 7 days. |
| BG005 | Sequence 3b | Sequence 3,2,1: Both simeprevir and dolutegravir, then dolutegravir only, then simeprevir only. dolutegravir: dolutegravir tablets 50mg, once daily x 7 days. simeprevir: simeprevir tablets 150mg, once daily x 7 days. |
| BG006 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| Primary | Dolutegravir AUC Pharmacokinetics | Determine Dolutegravir area-under-the concentration time curve (AUC) when administered alone and when co-administered with simeprevir. | Only arms that included Dolutegravir administration are included. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | Pre-dose and, 1, 2, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose on day 7 |
|
|
|
| 25 |
| 0 |
| 25 |
| 4 |
| 25 |
| EG001 | Dolutegravir Only | Dolutegravir tablets 50mg, once daily x 7 days. | 0 | 24 | 0 | 24 | 7 | 24 |
| EG002 | Dolutegravir and Simeprevir Co-administered: | Dolutegravir and simeprevir co-administered: dolutegravir tablets 50mg, once daily, and simeprevir tablets 150mg, once daily, x 7 days | 0 | 24 | 0 | 24 | 10 | 24 |
| Gastrointestinal issues (stomach pain, gas, vomiting, nausea, diarrhea) | Gastrointestinal disorders | Systematic Assessment |
|
| Fatigue | General disorders | Systematic Assessment |
|
| Photosensitivity | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Abnormal Labs | General disorders | Systematic Assessment |
|
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| D014777 |
| Virus Diseases |
| D018178 | Flaviviridae Infections |
| D012327 | RNA Virus Infections |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D006575 |
| Heterocyclic Compounds, 3-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |