Clinical drug investigation
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Randomized Controlled Trial
Exposure-Efficacy Analyses of Ombitasvir, Paritaprevir/Ritonavir with Dasabuvir ± Ribavirin in HCV Genotype 1-Infected Patients.
The three-direct-acting antiviral (DAA) combination regimen of ombitasvir, paritaprevir (coadministered with ritonavir [paritaprevir/ritonavir], and dasabuvir (the 3D regimen) ± ribavirin for treatment of HCV genotype 1-infected patients demonstrated efficacy and safety in Phase II and Phase III clinical trials. The relationships between the steady-state exposure (area under the concentration-time curve at steady state and trough concentration at steady state) of the three DAAs and ribavirin with sustained virologic response at 12 weeks after treatment (SVR12) following administration of the 3D regimen in six Phase II/III studies were examined. ⋯ The results of these analyses indicate that the doses selected for the 3D regimen were optimal, achieving high SVR12 rates across the range of exposures observed in the Phase III studies.
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Randomized Controlled Trial
Combination therapy with milrinone and esmolol for heart protection in patients with severe sepsis: a prospective, randomized trial.
As a β-adrenoceptor antagonist (β-blocker), esmolol can reduce cardiac output and the phosphodiesterase III inhibitor milrinone has been shown to improve heart contractility in patients with septic shock. This study was performed to assess the effects of esmolol combined with milrinone in patients with severe sepsis. ⋯ Combination therapy with milrinone and esmolol could improve cardiac function and the 28-day survival rate in patients with severe sepsis.
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Randomized Controlled Trial
Assessment of Alcohol-Induced Dose Dumping with a Hydrocodone Bitartrate Extended-Release Tablet Formulated with CIMA(®) Abuse Deterrence Technology.
Greater drug content requirements for extended-release (ER) opioids necessitate greater protection against dose dumping. Hydrocodone ER employs the CIMA(®) Abuse-Deterrence Technology platform, which provides resistance against rapid release of the active moiety when the tablet is manipulated or taken with alcohol. ⋯ Hydrocodone ER tablets were resistant to dose dumping when administered with alcohol in healthy subjects based on similar systemic exposures observed across all treatments.
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Randomized Controlled Trial
A novel once-daily fixed-dose combination of memantine extended release and donepezil for the treatment of moderate to severe Alzheimer's disease: two phase I studies in healthy volunteers.
Combining two standard-of-care medications for Alzheimer's disease (AD) into a single once-daily dosage unit may improve treatment adherence, facilitate drug administration, and reduce caregiver burden. A new fixed-dose combination (FDC) capsule containing 28 mg memantine extended release (ER) and 10 mg donepezil was evaluated for bioequivalence with co-administered commercially available memantine ER and donepezil, and for bioavailability with regard to food intake. ⋯ An FDC capsule containing 28 mg memantine ER and 10 mg donepezil is bioequivalent to commercially available memantine ER and donepezil, and bioavailability is not affected by food intake or sprinkling of capsule contents on applesauce.
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Randomized Controlled Trial
Safety, Tolerability and Pharmacokinetic and Pharmacodynamic Learnings from a Double-Blind, Randomized, Placebo-Controlled, Sequential Group First-in-Human Study of the TRPV1 Antagonist, JNJ-38893777, in Healthy Men.
Nociceptive and neuropathic pain, one of common reasons of disability and loss of quality life, are often undertreated due to safety concerns with current therapies. This study assessed the safety, tolerability, pharmacokinetics and pharmacodynamics of JNJ-38893777, a potent and selective transient receptor potential vanilloid 1 (TRPV1) channel antagonist in healthy men. ⋯ JNJ-38893777 was tolerated at single doses up to 500 mg (fed) and is suitable for further clinical development.