John Aspegren - Academia.edu (original) (raw)

Papers by John Aspegren

Animals

Cats frequently suffer from anxiety related to travel and veterinary visits. One sequela is avoid... more Cats frequently suffer from anxiety related to travel and veterinary visits. One sequela is avoidance of veterinary visits and lack of adequate veterinary care. The objective of this study was to test clinical efficacy and safety of a novel formulation of a pregabalin 50 mg/mL oral solution for alleviation of anxiety and fear in cats during transport and veterinary visits. A total of 209 client-owned cats were given either a flavored pregabalin oral solution at the dosage of 5 mg/kg (n = 108) or an identical placebo (n = 101) approximately 90 min before placing them into the carrier and transporting them in a car for at least 20 min to a veterinary clinic. The treatment effect using a 5-point numerical rating scale was evaluated during transportation by the owner and during clinical examination by the veterinarian, both blinded to the treatment. In addition, to verify the owner assessment, an external expert blinded to the treatment and owner assessment evaluated the transportation ...

Wiley-Blackwell, 2009

Pitkä julkaisu CD:llä Abstract #350vo

BSAVA Congress 2021: Clinical abstract presentations, 2021

Objectives Diabetes mellitus (DM) is a common condition that markedly impacts quality of pet cats... more Objectives Diabetes mellitus (DM) is a common condition that markedly impacts quality of pet cats and dogs. The aim of this study was to identify DM-associated perturbations in the feline pancreatic islet microenvironment. The utility of "clear, unobstructed brain imaging cocktails and computational analysis" (CUBIC) for three-dimensional (3D) pancreatic analysis was investigated.

Animals, 2023

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

European Journal of Pharmaceutics and Biopharmaceutics

European Journal of Pharmacology

The pharmacological profile of tasipimidine, a novel orally active α2-adrenoceptor agonist develo... more The pharmacological profile of tasipimidine, a novel orally active α2-adrenoceptor agonist developed for situational anxiety and fear in dogs, was studied in various in vitro and in vivo models. In the cell assays, tasipimidine demonstrated binding affinity and full agonism on the human α2A-adrenoceptors with a pEC50 of 7.57, while agonism on the α2B-and α2C-adrenoceptors and the rodent α2D-adrenoceptor was weaker, resulting in pEC50 values of 6.00, 6.29 and 6.56, respectively. Tasipimidine had a low binding affinity on the human α1-adrenoceptors. It had no functional effects in the LNCaP cells expressing endogenously the human α1A-adrenoceptors but was a weak agonist in the Chem-1 cells coexpressing Gα15 protein and α1A-adrenoceptors. In the recombinant CHO cells, although tasipimidine was a weak partial agonist in the inositol monophosphate accumulation assay, it was a full agonist in the intracellular [Ca2+] assay. No functional effects were observed on the human α1B-adrenoceptor, whereas in the rat α1A and α1B-adrenoceptors, tasipimidine was a weak partial agonist. In the rat vas deferens preparations, tasipimidine was a full agonist on the α2D-adrenoceptor but weak partial agonist on the α1-adrenoceptor. The receptor profile of tasipimidine indicated few secondary targets, and no functional effects were observed. Sedative effects of tasipimidine were demonstrated in vivo by the reduced acoustic startle reflex in rats with subcutaneous doses and decreased spontaneous locomotor activity in mice with subcutaneous and higher oral doses. It may be concluded that tasipimidine is an orally active and selective α2A-adrenoceptor agonist.

Proceedings of the 11th International Veterinary Behaviour Meeting, 14-16th September 2017, Samorin, Slovakia, 2017

Frontiers in Veterinary Science, 2021

Objectives: The aim of this clinical pilot study was to evaluate the dosage, efficacy, and clinic... more Objectives: The aim of this clinical pilot study was to evaluate the dosage, efficacy, and clinical safety of a single oral dose of pregabalin in cats that experience fear and anxiety when placed into a carrier and transported by car.Methods: Thirteen client-owned cats were enrolled in a blinded, randomized, crossover study with three treatment days approximately 1 week apart. The cats were assigned to receive pregabalin oral solution at dosages of 5 and 10 mg/kg and placebo in a randomized order, one treatment per week. Treatment was administered ~90 min before placing the cat into a carrier and starting transportation. Efficacy was assessed by the owners using a categorical scale and, based on video recordings, by an external observer, both blinded to the treatment.Results: Owners assessed that cats given pregabalin displayed less vocalization, restlessness, and panting during transportation than did cats given placebo. Correlation between owners' and external observer's a...

Veterinary Record, 2021

INTRODUCTION Many dogs are anxious and/or fearful in veterinary clinics and exhibit avoidant and/... more INTRODUCTION Many dogs are anxious and/or fearful in veterinary clinics and exhibit avoidant and/or defensive behaviour. The purpose of pharmacological interventions is to reduce anxiety and to enable patient-friendly, low stress physical examination and procedures. MATERIALS AND METHODS This was a randomised, double-blind, placebo-controlled, parallel-group, multicentre, clinical-field study. The eligible dogs (n = 76) were randomly assigned to receive dexmedetomidine 0.1 mg/g oromucosal gel at a dose of 125 μg/m2 (n = 27) or 250 μg/m2 (n = 24), or an equivalent volume of placebo gel (n = 23). RESULTS The investigator's ability to perform the intended procedure (physical examination and 1 short minor veterinary or husbandry procedure) was excellent for 40.7% of the dogs that received dexmedetomidine 125 μg/m2 and 33.3% of those that received dexmedetomidine 250 μg/m2 compared to only 4.3% of the placebo dogs. The overall treatment effect was statistically significant (p = 0.03). In addition, the investigators subjective stress level assessments revealed that dexmedetomidine treated dogs showed significantly more commonly relaxed body posture (p < 0.01) and more relaxed behaviour when entering the examination room (p = 0.02). There were very few adverse events, and treated animals were not sedated. CONCLUSIONS This study indicated a beneficial treatment effect of dexmedetomidine gel in alleviation of canine fear and anxiety during minor veterinary or husbandry procedures in the clinic environment in dogs previously reported to suffer from fear and anxiety during veterinary visits. Both dexmedetomidine gel doses studied were effective, and no clinical safety concerns were noticed for either dose.

Journal of Clinical Oncology, 2022

90 Background: Darolutamide, a structurally distinct and highly potent androgen receptor inhibito... more 90 Background: Darolutamide, a structurally distinct and highly potent androgen receptor inhibitor, had a consistently favorable safety and tolerability profile in patients with nonmetastatic castration-resistant prostate cancer in ARAMIS, and discontinuation rates due to adverse events (AEs) remained consistently low after longer follow-up. In previously reported phase 1/2 studies in patients with metastatic castration-resistant prostate cancer (mCRPC), darolutamide was well tolerated for up to 25 months. We report the safety and tolerability of extended treatment with darolutamide in these mCRPC studies. Methods: Data from three phase 1/2 studies (NCT02363855, NCT01317641/NCT01429064, and NCT01784757) in patients with mCRPC were pooled for analysis of long-term safety. Results are summarized descriptively. Results: Of 173 patients with mCRPC evaluable for safety in the 3 studies, 13 patients received > 2 years of darolutamide treatment; median duration of treatment was 38 month...

The Journal of Urology, 2016

total and free T, sex hormone binding globulin (SHBG), bone turnover markers and hot flashes. RES... more total and free T, sex hormone binding globulin (SHBG), bone turnover markers and hot flashes. RESULTS: The 250 mg cohort (n¼39) has completed the time period for assessment of the primary endpoint. Ten of the 39 (26%) subjects exhibited a 50% decrease in PSA by Day 90, with 11/39 (28%) by Day 120, while 18/39 (46%) had PSA declines of 30%. Median SHBG levels increased 301% of baseline, confirming the principal mechanism of drug action. While on study, median free T decreases of 44% were observed across all subjects and 20/26 (77%) of the subjects with baseline serum free T levels >0.7 pg/ml fell below this level. Therefore, 250 mg GTx-758 decreased free testosterone levels in an additive fashion to their existing LHRH therapy. The bone turnover biomarker, C-telopeptide, decreased in 79% of the subjects. 250 mg of GTx-758 has been generally well tolerated with two reported possibly drug related SAEs (VTE and MI). CONCLUSIONS: In this Phase 2 trial, 250 mg daily GTx-758 has activity, likely mediated by lowering free T levels in patients with CRPC on LHRH therapy, and may provide amelioration of estrogen deficiency side effects associated with ADT.

European Urology Focus, 2016

Background: ODM-201, a new-generation androgen receptor inhibitor, has shown clinical efficacy in... more Background: ODM-201, a new-generation androgen receptor inhibitor, has shown clinical efficacy in prostate cancer (PCa). Quantitative methods are needed to accurately assess changes in bone as a measurement of treatment response. The Bone Scan Index (BSI) reflects the percentage of skeletal mass a given tumour affects. Objective: To evaluate the predictive value of the BSI in metastatic castration-resistant PCa (mCRPC) patients undergoing treatment with ODM-201. Design, setting, and participants: From a total of 134 mCRPC patients who participated in the Activity and Safety of ODM-201 in Patients with Progressive Metastatic Castration-resistant Prostate Cancer clinical trial and received ODM-201, we retrospectively selected all those patients who had bone scan image data of sufficient quality to allow for both baseline and 12-wk follow-up BSI-assessments (n = 47). We used the automated EXINI bone BSI software (EXINI Diagnostics AB, Lund, Sweden) to obtain BSI data. Outcome measurements and statistical analysis: We used the Cox proportional hazards model and Kaplan-Meier estimates to investigate the association among BSI, traditional clinical parameters, disease progression, and radiographic progression-free survival (rPFS). Results and limitations: In the BSI assessments, at follow-up, patients who had a decrease or at most a 20% increase from BSI baseline had a significantly longer time to progression in bone (median not reached vs 23 wk, hazard ratio [HR]: 0.20; 95% confidence interval [CI], 0.07-0.58; p = 0.003) and rPFS (median: 50 wk vs 14 wk; HR: 0.35; 95% CI, 0.17-0.74; p = 0.006) than those who had a BSI increase >20% during treatment. Conclusions: The on-treatment change in BSI was significantly associated with rPFS in mCRPC patients, and an increase >20% in BSI predicted reduced rPFS. BSI for quantification of bone metastases may be a valuable complementary method for evaluation of treatment response in mCRPC patients. Patient summary: An increase in Bone Scan Index (BSI) was associated with shorter time to disease progression in patients treated with ODM-201. BSI may be a valuable method of complementing treatment response evaluation in patients with advanced prostate cancer.

The aim of this pilot study was to investigate the anxiolytic effect of two doses of dexmedetomid... more The aim of this pilot study was to investigate the anxiolytic effect of two doses of dexmedetomidine in dogs with a history of acute fear and anxiety associated with fireworks. Thirty-six clinically healthy (ASA I and II) privately-owned dogs were enrolled in a randomised, double-blind, placebo-controlled clinical field study conducted at New Year´s Eve in Finland. Dexmedetomidine (n=24) at doses 125 μg/m2 (n=12) or 250 μg/m2 (n=12) or placebo (n=12) oromucosal gel was administered up to five times as needed, with a minimum dosing interval of two hours. Owners’ assessment of treatment effect, dog’s alertness, easiness of administration, status of oral mucosa and adverse events were recorded. The study was performed in the home of each dog without restrictions on feeding or walking the dogs during the study. Treatment effect was analysed with Fisher’s exact test and all results were also analysed descriptively. All dog owners assessed the gel to be very or quite easy to administer. T...

Amlodipine has been considered the treatment of choice for hypertension in cats for more than a d... more Amlodipine has been considered the treatment of choice for hypertension in cats for more than a decade. There is, however, an unmet need for a cat-specific formulation. The aim of the study was to assess the efficacy of chewable amlodipine tablets in reducing systolic blood pressure (SBP) in cats diagnosed with hypertension. Seventy-seven client-owned cats were included in the study (mean age 14 years). The study was randomised, double-blind, placebo controlled, and consisted of two phases. In the blinded phase, 42 cats received 0.125 mg/kg amlodipine once daily for 14 days. If they responded the dose remained the same to day 28. For non-responders, the dose was increased to 0.25 mg/kg. Thirty-five cats received placebo following the same protocol. Arterial blood pressure was measured using a high definition oscillometry method. At day 28 a responder was defined as a cat showing a decrease of SBP to ≤150 mmHg or a decrease from baseline of at least 15%. After 28 days all cats contin...

The Lancet. Oncology, 2014

ODM-201 is a novel androgen receptor (AR) inhibitor designed to block the growth of prostate canc... more ODM-201 is a novel androgen receptor (AR) inhibitor designed to block the growth of prostate cancer cells through high-affinity binding to the AR and inhibition of AR nuclear translocation. This trial assessed ODM-201's safety, pharmacokinetics, and activity in men with metastatic castration-resistant prostate cancer. The ARADES trial is an open-label phase 1-2 trial undertaken in 23 hospitals across Europe and USA with ongoing long-term follow-up. Men with progressive metastatic castration-resistant prostate cancer, who had castrate concentrations of testosterone and an Eastern Cooperative Oncology Group score of 0-1 were enrolled. In the phase 1 part of the trial, patients were given oral ODM-201 at a starting daily dose of 200 mg, which was increased to 400 mg, 600 mg, 1000 mg, 1400 mg, and 1800 mg. In phase 2, patients were randomly assigned centrally and stratified by previous chemotherapy and treatment with CPY17 inhibitors, to receive one of three daily doses of ODM-201 (...

Journal of Clinical Oncology

102^ Background: ODM-201 is a novel potent full androgen receptor (AR) inhibitor for CRPC. ODM-20... more 102^ Background: ODM-201 is a novel potent full androgen receptor (AR) inhibitor for CRPC. ODM-201 has excellent nonclinical efficacy in xenograft studies and high PSA response rate in CYP17i-naïve CRPC patients in the phase I/II ARADES study. Methods: To further analyze clinical efficacy of ODM-201 in CRPC pts we evaluated the overall response rate (ORR) in ARADES phase I/II study (Fizazi et al. #2853, ECC2013, Amsterdam 28 Sept 2013 ).Patients (pts) were enrolled into three dose levels 100mg bid, 200mg bid and 700mg bid. Results: All eligible 124 pts had progressive mCRPC; 37 pts were pre-chemo/CYP17i-naïve, 32 post-chemo/CYP17i-naïve and 55 post-CYP17i. Thirty-two (86%) pts in the pre-chemo/CYP17i-naïve group, 27 (84%) post-chemo/CYP17i-naïve and 48 (87%) post-CYP17i had bone disease at baseline. Similarly, twenty-two (29%) pts, 19 (59%) and 36 (65%), respectively had RECIST-define measurable disease. Median baseline PSA was 101ng/mL (3-1294) in pre-chemo/CYP17-i-naïve group, 94n...

European Urology Supplements, 2014