Expedition 3 Trial

Achaia Taltoan, Mercer University College of Pharmacy

Alzheimer’s disease (AD) involves the development of extracellular amyloid beta (Aβ) plaques and intracellular fibrous tangles of tau protein. [1] The Aβ hypothesis postulates that overproduction or reduced clearance of Aβ from the cerebrum leads to formation of Aβ plaques, resulting in the cognitive deficits of Alzheimer’s disease. [1] Solanezumab is a humanized G1 monoclonal antibody that binds to Aβ peptides to increase clearance from the brain.[2] The Expedition and Expedition 2 trials evaluated the use of solanezumab in mild to moderate Alzheimer’s disease; pooled secondary analyses demonstrated a significant improvement in functional and cognitive decline in mild Alzheimer’s disease patients.[3] The Expedition 3 trial seeks to clarify the findings of the previous Expedition trials through limiting the population to mild Alzheimer’s disease patients.

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Vitamin D and Nifedipine in Preeclampsia

Achaia Taltoan, Mercer University College of Pharmacy

Preeclampsia is a syndrome characterized by a persistent blood pressure ≥ 140/90 mmHg and urine protein ≥ 300 mg/24 hours after 20 weeks of gestation. The American College of Obstetrics and Gynecology guidelines on pregnancy induced hypertension recommend immediate release nifedipine as one of the first line agents for treatment of blood pressure ≥ 160/110 mmHg. [1]

Although the pathogenesis of preeclampsia is unclear, some evidence suggests that vitamin D plays a role in the emergence of preeclampsia. [2] It is thought that vitamin D deficiency is associated with increased TNF-α and decreased IL-10 that are linked to hypertension during pregnancy and preterm birth. [2] The role of vitamin D as an antihypertensive agent for preeclampsia has not been assessed in human patients until this trial was conducted. [3]

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Novel Therapeutic Option Striking Multiple Downstream Inflammatory Pathways Associated with Uncontrollable Asthma

JoAnn Filipov, Mercer University College of Pharmacy

Despite established standard of care therapies, literature suggests that patients diagnosed with moderate-to-severe asthma experience frequent exacerbations and significant lung function limitations due to uncontrolled asthma. [1] A proposed molecular mechanism in asthma is the type 2 (T2) inflammatory pathway, characterized by elevated levels of blood eosinophils, serum IgE, and fractional exhaled nitric oxide (FENO). [2] Thymic stromal lymphopoietin (TSLP) is an epithelial cytokine central for regulation of T2 immunity.  It has been identified as a potential therapeutic target for its ability to activate various cell types, such as basophils, mast cells, innate lymphoid cells, natural killer T cells, and neutrophils, across a broad patient population. [3]

Tezepelumab is an investigational human IgG2 monoclonal antibody. It binds to TSLP to prevent TSLP-receptor interaction. [4] This mechanism prevents the release of cytokines via immune cells targeted by TSLP early in the inflammation cascade. [5] It has been suggested that tezepelumab could be an adjunct therapy for patients with a history of asthma exacerbations and uncontrolled asthma who have failed previous therapies. [6]

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A Possible New Drug for Postmenopausal Osteoporosis

Tibin K. Titus, Mercer University College of Pharmacy

Postmenopausal osteoporosis occurs due to estrogen deficiency resulting in an increase of mature osteoclasts, which will increase bone resorption into the blood. [1] Simultaneously, there is a decrease in calcium absorption and increase in calcium excretion through the gut. [1] Romosozumab is a new monoclonal antibody that is in development for treatment of osteoporosis in postmenopausal women at increased risk of fractures. [2] In a previous trial, romosozumab reduced the risk of fracture compared to placebo; however, it has not been compared with an active comparator. [2] This study was conducted with an active comparator, alendronate, to compare the two drugs for fracture prevention in postmenopausal women with osteoporosis. [3]

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Adasuve for the Rapid Treatment of Agitation in Schizophrenia

JoAnn Filipov, Mercer University College of Pharmacy

Limited options of antipsychotic drug administration exist in the current standard of care for the acute treatment of agitation. [1] According to the Expert Consensus Guidelines for Treatment of Behavioral Emergencies, speed of onset is key in choosing medication administration route. [2] Since intravenous administration of antipsychotics necessitates established intravenous access, oral and intramuscular administrations are more prominently used. However, oral and intramuscular formulations have a more gradual onset of action, unlike intravenous pharmacokinetics, thus allowing for symptoms to escalate before they begin to resolve. [3] It is reported that patients with an episode of acute agitation often resist intramuscular administration, further escalating the risk of intensifying symptoms. Therefore, there is a need for anti-agitation medications with rapid onset of action and acceptable safety profile that are easy to administer. [4]

Loxapine, an antipsychotic indicated for the treatment of schizophrenia. [5] Loxapine is available as a capsule and intramuscular injection formulations, that have demonstrated efficacy in the treatment of agitation. [6] Due to the unmet need, a new formulation of loxapine, AdasuveÒ, was developed that can be inhaled via Staccato inhalation system. The system is shown to distribute loxapine with intravenous-like pharmacokinetics. [7] Below article summarized the efficacy and safety of Adasuve®. [8]

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Efficacy, Acceptability, and Safety of Atypical Antipsychotics in First Episode Schizophrenia

Achaia Taltoan, Mercer University College of Pharmacy

The American Psychiatric Association (APA) schizophrenia guidelines recommend all second-generation (“atypical”) antipsychotics as first-line treatment for first episode schizophrenia. [1] Unlike the APA guidelines, the 2009 schizophrenia PORT statements recommend risperidone, quetiapine, aripiprazole, and ziprasidone as first line therapy but not olanzapine due to the associated metabolic side effects. [2]

While trials such as the EUFEST and the CATIE trial have compared second-generation antipsychotics to first-generation antipsychotics, there is a lack of guidance whether one second-generation antipsychotic is better than the other in certain situations for the treatment of first episode schizophrenia. [3] This trial attempts to provide data to enhance the understanding of the efficacy, discontinuation rate, and adverse events of the second-generation antipsychotics in comparison with one another.

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A Novel drug, Ingrezza, for the Treatment of Tardive Dyskinesia

JoAnn Filipov, Mercer University College of Pharmacy

Tardive Dyskinesia is an involuntary movement disorder induced by continued exposure to dopamine receptor agents (DBRAs). It is associated with persistent, hindering physical conditions causing significant problems for psychiatric patients. [1] Second-generation (“atypical”) antipsychotics were thought have a decreased risk for tardive dyskinesia compared to first-generation antipsychotics, but current literature indicates the risk may be increased with both generations. [2] For management, the two main methods are: 1) reduce the antipsychotic dose or 2) discontinue the drug. However, literature suggests both may not be the best strategies as they may lead to suboptimal management of the psychiatric illness without resolving tardive dyskinesia. [3]

Vesicular monoamine transporter 2 (VMAT 2) inhibitors (e.g. tetrabenazine) have been used to treat movement-related symptoms of Huntington’s disease. [4] They regulate presynaptic packaging and dopamine release into the synapse. Due to this mechanism of action, it was proposed that VMAT2 inhibitors may be able to counterbalance involuntary movement side effects of antipsychotics. [5] Research sparked to develop valbenazine (Ingrezza Ò). Its exact mechanism of action is unknown; however, it is thought to reversibly inhibit VMAT2. [6] In 2017, the Food and Drug Administration approved valbenazine for the treatment of tardive dyskinesia in adults. Below summarizes the phase 3 trial of valbenazine. [7]

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