Clinical Therapeutics e4 Volume 38 Number 10S 1.11 INCONSISTENCY IN PRECLINICAL AND CLINICAL TRIALS EXPLORING THE ROLE OF HORMONE REPLACEMENT THERAPY IN ALZHEIMER’S DISEASE J. Osmanovic-Barilar; and M. Salkovic-Petrisic University of Zagreb School of Medicine, Zagreb, Croatia Introduction: Hormone replacement therapy (HRT) is widely pre- scribed in women during or after menopausal transition to replace decline in estrogen (E) and progesterone (P4) level. While some stud- ies indicate that E and P4 depletion in postmenopausal women might carry a significant risk for developing sporadic Alzheimer’s disease (sAD), which may be reduced by E-based HRT, recent clinical trials oppose the beneficial effect of such therapy. We aimed to explore possible reasons for such inconsistency in preclinical and clinical trials on HRT in AD condition. Methods: PUBMED database (reviews, meta-analysis, and original papers) was searched (1994-2016) by using the following keywords: HRT, E, P4, AD, menopause, and cognition. Results: An overview of literature search revealed that possible rea- sons for such inconsistency can be found both in preclinical and clinical trials as well as in the HRT itself, roughly classified as follows: 1. Inappropriate animal models that result in incorrect translation of animal-to-human or human-to-animal condition regarding the type of sex hormone depletion (abrupt/surgical removal of gonads or gradual/physiological exhaustion of gonads) and regarding the AD form (widely exploited transgenic models represent rare famil- iar but not prevailing sAD form) 2. Heterogeneous postmenopausal women groups in clinical tri- als (regarding the sAD stage or anti-AD and concomitant drug therapy and hysterectomy status) 3. Incomparable HRT treatment design in/within preclinical and clinical trials (different estrogen/progestogen compounds and dose, route of administration, pharmaceutical formulation, and timing of treatment initiation) Conclusion: To answer the question on possible beneficial effect of HRT in postmenopausal women with sAD, further research is needed both in humans and animals that will take all mentioned issues into account and additionally focus on other types of estrogen and pro- gestogen compounds, including progestins like norprogesterones, levonorgestrel, and selective modulators of estrogen receptors. 1.12 THE EFFECTS OF SENS-111, A NEW H4R ANTAGONIST, ON VERTIGO INDUCED BY CALORIC TEST IN HEALTHY VOLUNTEERS (HV) IS RELATED TO PLASMA CONCENTRATIONS P. Attali 1,2,3,4 ; R. Gomeni 1,2,3,4 ; E. Wersinger 1,2,3,4 ; S. Poli 1,2,3,4 ; and F. Venail 1,2,3,4 1 Sensorion, Montpellier, France; 2 Pharmacometrica, La Fouillade, France; 3 Consultant in Pharmacokinetics, Geneva, Switzerland; and 4 Hopital Gui de Chaulliac, Montpellier, France Background: SENS-111, a new selective nonsedative H4R antago- nist, was reported to reduce vertigo induced by a caloric irrigation in HV. However, no optimal daily dose from 50 to 250 mg/d for 4-7 days could be identified due to the large inter- and intra-variability of symptoms induced by the caloric irrigation. The relationship between PK parameters and the effects on vestibular symptoms was thus investigated. Methods: Five cohorts of 12 HV were given either a capsule of SENS- 111 (9 subjects/cohort) or placebo (3 subjects) orally once daily for 4 days (50, 100, 150 mg/d) or 7 days (200 and 250 mg/d) according to a randomized double-blind dose escalating design. Following 3 base- line recordings at 3h interval before treatment, nystagmus (latency, duration, frequency) and vertigo symptoms were evaluated daily 2 hours post dosing using video nystagmography, questionnaires (latency, duration of appearance/disappearance), Visual Analog Scale (intensity), and European Evaluation Vertigo Scale. A population PK analysis was conducted on all data collected in the study. Then, two descriptive PK/PD analyses were conducted on the change from baseline values considering the SENS-111 exposure up to 500 ng/mL and up to 1000 ng/mL. Finally, a model based approach was devel- oped to account for the individual trajectories of the response. Results: The latency of vertigo appearance increased with exposure at concentrations below 500 ng/mL (p=0.0367) while it decreased with concentrations ranging from 500 to 1000 ng/mL. Similarly, the duration of vertigo decreased with the increase of exposure (p=0.0455) at concentrations below 500 ng/mL while it increased with the exposure at concentration above 500 ng/mL. Data on other end points will also be presented. Conclusions: Vertigo end points were improved by SENS-111 up to concentrations of 500 ng/mL and then progressively deteriorated. This is consistent with preclinical findings and may be related to off-target effects at high concentrations. 1.13 ARE WE SCARED OF CLINICAL TRIALS IF NOT SUFFICIENTLY INFORMED AND EDUCATED? L. Burnazovic-Ristic; M. Rakanovic-Todic; S. Maleskic; A. Kulo Cesic; and J. Kusturica Medical Faculty University of Sarajevo, Sarajevo, Bosnia and Herzegovina Introduction: Clinical trials (CTs) are prospective biomedical research studies designed to answer specific questions about new treatments and already known interventions. Clinical trials are highly regulated by highest authorities and mainly generate data on safety and efficacy. Previous studies identified main barriers to participation in CTs as concerns of patients about provided information, safety, and costs. Usually medical curricula are not directed for wider edu- cation in this topic, but basic information is shared within several subjects. In this study we explored the basic knowledge and attitude about clinical trials among medical students, having in mind their further involvement in performing of trials as well as educating the community raising awareness about participation. Material and Methods: This study was designed as a cross-sectional, self-report online survey among medical students of Medical Faculty University of Sarajevo. Results: Among 142 students who completed questionnaire, 72.5% did not respond to a question about their own satisfaction with the knowledge about CTs. Majority of the students were unfamiliar with awareness of conducting international clinical trials in Bosnia and Herzegovina (71.8%) and getting transparent information on a web page of Regulatory Drug Agency (80%). They had an overall positive attitude toward importance of CTs in education of health professionals with 85% of answers with sub-maximum and maximum score. However, only 38% would participate in a CT. Conclusions: Overall, the medical students showed insufficient knowledge and lack of awareness about CTs. Similar findings are described in literature as major barriers to recruitment and enrolment of patients. Specific areas of deficient knowledge are recognized, and these results could be useful as a general guidance for curriculum