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This is a research study to evaluate the safety, tolerability and anti-viral activity of GS-9669 in patients with Hepatitis C infection.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Multiple-dose, dose-escalation study of GS-9669 | Experimental | Multiple-dose, dose-escalation study of GS-9669, a nonnucleotide NS5B inhibitor of hepatitis C virus (HCV), in subjects with chronic HCV infection. Dosing is planned in up to 7 unique dosing cohorts. Each cohort will be comprised of 10 genotype 1a (Cohorts 1, 2, 3, 4, and 5) or genotype 1b (Cohort 6 and 7), with eight subjects randomized to receive active drug and two subjects randomized to receive placebo per cohort. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GS-9669 tablets | Drug |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Safety and Tolerability | To evaluate safety and tolerability of escalating multiple oral doses of GS 9669. Safety will be assessed during the study through the reporting of adverse events, clinical laboratory tests, physical examinations, vital signs, and 12-lead ECGs at various time points during the study. | through 24 weeks of off-treatment follow-up |
| Antiviral Activity | To evaluate antiviral activity of GS-9669 against HCV in genotype-1a and 1b (GT1a/b) subjects. This will be evaluated using change from baseline in plasma HCV RNA. Reduction in HCV RNA will be summarized as categorical (as < 1, ≥ 1 to <2, ≥ 2 to <3, or ≥ 3 log10 IU/mL) reduction from baseline. | through 24 weeks of off-treatment follow-up |
| Measure | Description | Time Frame |
|---|---|---|
| Viral Dynamics and Pharmacodynamics | To characterize the viral dynamics of GS-9669. The median change from baseline in HCV RNA and time-weighted average change from baseline through Day 3 will be assessed based on plasma HCV RNA sampling times to characterize the viral dynamics of GS-9669. | Through 17 days of therapy |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Stephen Rossi, PharmD | Gilead Sciences | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Impact Clinical Trials | Los Angeles | California | 90036 | United States | ||
| Avail Clinical Research, LLC |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25155588 | Derived | Dvory-Sobol H, Voitenleitner C, Mabery E, Skurnac T, Lawitz EJ, McHutchison J, Svarovskaia ES, Delaney W, Miller MD, Mo H. Clinical and in vitro resistance to GS-9669, a thumb site II nonnucleoside inhibitor of the hepatitis C virus NS5B polymerase. Antimicrob Agents Chemother. 2014 Nov;58(11):6599-606. doi: 10.1128/AAC.02815-14. Epub 2014 Aug 25. | |
| 23183437 |
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| Placebo to Match GS-9669 tablet | Drug |
|
| composite of Pharmacokinetics |
To characterize the plasma PK parameters of GS-9669. The secondary PK endpoints will be evaluated using standard non-compartmental methods. Relevant PK parameters will be determined using standard non-compartmental methods with the linear-logarithmic trapezoidal rule utilizing a PK data analysis program (e.g., WinNonlin®) for GS-9669 as appropriate: Cmax, Tmax, Clast, Tlast, Ctau, λz, AUC0-last, AUCtau, , CL/F, and T½. |
| Through 17 days of therapy |
| Genotypic Changes | To characterize genotypic changes from baseline in the NS5B coding region of HCV following multiple dose administration of GS-9669 and for up to 24 weeks thereafter | through 24 weeks of off-treatment follow-up |
| DeLand |
| Florida |
| 32720 |
| United States |
| Orlando Clinical Research Center | Orlando | Florida | 32809 | United States |
| Impact Clinical Trials | Las Vegas | Nevada | 89106 | United States |
| CRI Worldwide | Willingboro | New Jersey | 08046 | United States |
| CRI Worldwide | Philadelphia | Pennsylvania | 19139 | United States |
| Alamo Medical Research | San Antonio | Texas | 78215 | United States |
| Lifetree Clinical Research, LC | Salt Lake City | Utah | 84106 | United States |
| University of Utah Health Sciences Center | Salt Lake City | Utah | 84132 | United States |
| Charles River Clinical Services Northwest | Tacoma | Washington | 98418 | United States |
| Fundacion de Investigacion de Diego | San Juan | 00927 | Puerto Rico |
| Fenaux M, Eng S, Leavitt SA, Lee YJ, Mabery EM, Tian Y, Byun D, Canales E, Clarke MO, Doerffler E, Lazerwith SE, Lew W, Liu Q, Mertzman M, Morganelli P, Xu L, Ye H, Zhang J, Matles M, Murray BP, Mwangi J, Zhang J, Hashash A, Krawczyk SH, Bidgood AM, Appleby TC, Watkins WJ. Preclinical characterization of GS-9669, a thumb site II inhibitor of the hepatitis C virus NS5B polymerase. Antimicrob Agents Chemother. 2013 Feb;57(2):804-10. doi: 10.1128/AAC.02052-12. Epub 2012 Nov 26. |
| ID | Term |
|---|---|
| D006526 | Hepatitis C |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D006525 | Hepatitis, Viral, Human |
| D014777 | Virus Diseases |
| D018178 | Flaviviridae Infections |
| D012327 | RNA Virus Infections |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| C582393 | GS-9669 |
| D005502 | Food |
| D003143 | Communication Devices for People with Disabilities |
| D000074584 | WW Domain-Containing Oxidoreductase |
| ID | Term |
|---|---|
| D000066888 | Diet, Food, and Nutrition |
| D010829 | Physiological Phenomena |
| D019602 | Food and Beverages |
| D012656 | Self-Help Devices |
| D004864 | Equipment and Supplies |
| D000074583 | Short Chain Dehydrogenase-Reductases |
| D064430 | NAD (+) and NADP (+) Dependent Alcohol Oxidoreductases |
| D000429 | Alcohol Oxidoreductases |
| D010088 | Oxidoreductases |
| D004798 | Enzymes |
| D045762 | Enzymes and Coenzymes |
| D025521 | Tumor Suppressor Proteins |
| D009363 | Neoplasm Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
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