Harvoni Case Study

1.0 INTRODUCTORY STATEMENT AND GENERAL INVESTIGATIONAL PLAN
1.1. Drug and Broad Objectives

Harvoni is a fixed-dose combination of ledipasvir and sofosbuvir for the treatment for the chronic hepatitis C. Ledipasvir is an inhibitor of the HCV NS5A protein, which is required for viral replication. Resistance selection in cell culture and cross-resistance studies indicate ledipasvir targets NS5A as its mode of action. Sofosbuvir is an inhibitor of the HCV NS5B RNA-dependent RNA polymerase, which is required for viral replication.
The objectives of the proposed clinical investigation is to assess the efficacy and safety of 12 and 24 weeks of oral dose of sofosbuvir and Ledipasvir combination in patients with HCV genotype 1. The planned duration
1.4. Overall Investigational Plan
Around 3% of the population is infected with Hepatitis C virus genotype 1, which can cause serious infections. More than 15% of infected end up with chronic infection which can cause liver failure. All available treatment options for a patients involved interferon and ribavirin. In addition, there was no highly effective treatment for patients with hepatitis C who failed the treatment with interferon and ribavirin. Harvoni is a new drug where interferon and ribavirin is not required. New drug can improve patient lifestyle and duration of the treatment.[3]
The proposed 12 weeks open-label trial is designed to determine the ability of Harvoni oral tablets administered one tablet daily to target the replication of virus in patients with chronic Hepatitis C.
Secondary objective include evaluation of the safety, obtaining evidence of efficacy and effectiveness of new treatment over the existing standard treatment based on interferon and ribavirin. In phase I, participants with chronic hepatitis C will be divided in two groups. First group will be assigned to get a Harvoni tablets and the second group will be assigned to get a Harvoni tablet in combination with ribavirin for 12
3.0 CHEMISTRY, MANUFACTURING, AND CONTROL INFORMATION
3.1 Drug Substance:
Drug Substance of Harvoni is a combination of Ledipasvir and Sofosbuvir. Ledipasvir is a white to tinted, slightly hygroscopic crystalline solid which is Slightly solube in pH 2.3 buffer but partially insoluble in pH 4-7.5 buffers. This is Soluble in ethanol and DMSO but slightly soluble in acetone.
Sofosbuvir is a white to off-white non-hygroscopic crystalline solid which is slightly soluble in water (pH1.2-7.7). this is also soluble in ethanol, acetone, 2-propanol.[4]
3.2 Drug Product:
HARVONI is a fixed-dose combination tablet containing ledipasvir and sofosbuvir for oral administration. Ledipasvir is an HCV NS5A inhibitor and sofosbuvir is a nucleotide analog inhibitor of HCV NS5B polymerase. Each tablet contains 90 mg ledipasvir and 400 mg sofosbuvir. The tablets include the following inactive ingredients: colloidal silicon dioxide, copovidone, croscarmellose sodium, lactose monohydrate, magnesium stearate, and microcrystalline cellulose. The tablets are film-coated with a coating material containing the following inactive ingredients: FD&C yellow #6/sunset yellow FCF aluminum lake, polyethylene glycol,polyvinyl alcohol, talc, and titanium dioxide.