Pharmaceutical Product Development

About: Pharmaceutical Product Development is a company organization based out in Wilmington, North Carolina, United States. It is known for research contribution in the topics: Immunotoxin & Fusion protein. The organization has 402 authors who have published 353 publications receiving 16396 citations.

Prostacyclin Use Among Patients with Pulmonary Arterial Hypertension in the United States: A Retrospective Analysis of a Large Health Care Claims Database.

Abstract: BACKGROUND: Prostacyclins play an important role in the management of pulmonary arterial hypertension (PAH). Intravenous prostacyclin was the first disease-specific treatment for patients with PAH. Subcutaneous and nonparenteral (oral or inhaled) formulations have subsequently become available. However, data are lacking on how these different prostacyclin formulations are being used in clinical practice. OBJECTIVES: To (a) conduct retrospective analyses of a large U.S. health care claims database to describe the characteristics of patients with PAH initiating prostacyclin therapy, and (b) evaluate their treatment patterns, health care resource use, and associated costs. METHODS: Truven Commercial and Medicare databases were used to define annual cohorts of adults with PAH between January 1, 2010, and October 31, 2015. These patients were identified based on claims with ICD-9-CM diagnoses indicative of PAH (codes 416.0 or 416.8) and claims for PAH-specific medications and PAH-related procedures. Patients w...

Pharmacokinetics of saquinavir with atazanavir or low-dose ritonavir administered once daily (ASPIRE I) or twice daily (ASPIRE II) in seronegative volunteers.

Abstract: ASPIRE I and II were prospective, 3-way sequential crossover studies in healthy volunteers to compare the safety and pharmacokinetics of saquinavir/ritonavir (SQV/RTV) with saquinavir/atazanavir (SQV/ATV) administered either once daily (QD, ASPIRE I) or twice daily (BID, ASPIRE II). Treatments were separated by 10 days, and pharmacokinetic analyses were performed on days 11, 32, and 53. SQV pharmacokinetics were significantly higher when dosed with RTV compared to ATV (P < .05 for all comparisons). ATV pharmacokinetics were similar within treatment arms. ATV Cmin increased approximately 60%, and Cmax decreased approximately 35% with BID dosing compared with QD dosing. Women had higher exposure for all 3 protease inhibitors (PIs) compared with men after adjusting for weight. Adverse effects were primarily gastrointestinal-related with SQV/RTV and hyperbilirubinemia with SQV/ATV. Although SQV plasma concentrations were higher when coadministered with RTV, a combination of SQV/ATV administered BID may be a viable alternative in HIV-infected, PI-naive subjects intolerant to RTV.

Variability in Antinuclear Antibody Testing to Assess Patient Eligibility for Clinical Trials of Novel Treatments for Systemic Lupus Erythematosus.

Abstract: Objective In the development of novel therapies for systemic lupus erythematosus, antinuclear antibody (ANA) positivity represents a criterion for trial eligibility. Since as many as 30% of patients enrolled in trials have been ANA negative, we evaluated the performance characteristics of immunofluorescence assays (IFAs) for ANA determinations for screening. Methods This study used 5 commercially available IFAs to assess the ANA status of 181 patients enrolled in a phase II clinical trial for an anti-interleukin-6 antibody. Enrollment included a detailed review of medical records to verify a historical ANA value. IFA results were related to various clinical and serologic features at enrollment. Results While the frequency of ANA negativity assessed by the central laboratory was 23.8% in a cohort of 181 patients, the evaluated IFA kits demonstrated frequencies of negativity from 0.6 to 27.6%. With 2 IFA kits showing a significant frequency of ANA negativity, positive and negative samples differed in levels of anti-double-stranded DNA, C3, and presence of other ANAs as well as the frequency of high interferon (IFN) expression. Conclusion These findings indicate that, when used for screening, IFAs can vary because of performance characteristics of kits and thus can affect determination of trial eligibility. With kits producing a significant frequency of ANA negativity, ANA status can be associated with other serologic measures as well as the presence of the IFN signature, potentially affecting responsiveness to a trial agent.