scholarly journals Field study to investigate the effectiveness and safety of a novel orally administered combination drug product containing milbemycin oxime and lotilaner (Credelio® Plus) against natural intestinal nematode infections in dogs presented as veterinary patients in Europe

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Brad Hayes ◽  
Scott Wiseman ◽  
Daniel E. Snyder
Keyword(s):  
Field Study ◽  
Drug Product ◽  
Geometric Mean ◽  
Animal Health ◽  
Good Clinical Practice ◽  
Toxocara Canis ◽  
New Combination ◽  
Combination Drug ◽  
Milbemycin Oxime ◽  
Faecal Egg Counts

Abstract Background A randomised, blinded, positive controlled, multicentre, Good Clinical Practice-compliant, pivotal field study was conducted to evaluate the effectiveness and safety of a new combination of lotilaner + milbemycin oxime tablets (Credelio® Plus; Elanco Animal Health) administered orally to client-owned dogs naturally infected with intestinal nematodes. Methods Client-owned dogs presenting to veterinary clinics from households in France, Hungary and Germany were screened for intestinal nematodes. Dogs with an initial positive faecal egg count that was subsequently confirmed with a follow-up faecal examination to demonstrate the presence of naturally occurring mixed or mono-infections with Toxocara canis, Toxascaris leonina, Trichuris vulpis or Ancylostoma caninum were enrolled on Day 0 into the study. Households were randomised in an approximately 2:1 ratio to receive either an investigational product (IP; Credelio Plus tablets) or control product (CP; Nexgard Spectra® tablets) as treatment. Dogs were administered the IP (n = 278) or CP (n = 117) once on Day 0 at a dose rate of 0.75–1.56 mg/kg bodyweight milbemycin oxime and 20.0–41.5 mg/kg bodyweight lotilaner (IP) or as recommended (CP). Effectiveness of the IP and CP treatments was based on the post-treatment reduction in geometric mean faecal egg counts on Day 8 (range Day 7–10) after treatment as compared to their pre-treatment nematode faecal egg counts. Results Geometric mean (GM) faecal egg counts for T. canis, A caninum and T. vulpis were reduced by ≥ 97.2% in the Credelio Plus group and  by ≥ 95.3% in the afoxolaner + milbemycin oxime group. There were insufficient data to calculate a percentage reduction in GM faecal egg counts between Day 0 and Day 8 for T. leonina due to low prevalence. Credelio Plus was well tolerated in this field study. Of the 355 total doses administered, 82.3% were accepted free choice in the IP group compared to 80.8% in the CP group. Conclusions This study demonstrated effectiveness (≥ 97.2% reduction), safety and tablet acceptance of a combination of milbemycin oxime and lotilaner (Credelio Plus) administered orally to dogs with natural intestinal infections of T. canis, A. caninum and T. vulpis.

scholarly journals Field study to investigate the effectiveness and safety of a novel orally administered combination drug product containing milbemycin oxime and lotilaner (Credelio® Plus) for the prevention of heartworm disease (Dirofilaria immitis) in client-owned dogs in the USA

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Lisa M. Young ◽  
Scott Wiseman ◽  
Elizabeth Crawley ◽  
Kim Wallace ◽  
Daniel E. Snyder
Keyword(s):  
Field Study ◽  
Mississippi River ◽  
Dirofilaria Immitis ◽  
Drug Product ◽  
Clinical Effectiveness ◽  
Combination Product ◽  
Combination Drug ◽  
Milbemycin Oxime ◽  
Heartworm Disease ◽  
The Usa

Abstract Background Dirofilaria immitis, a globally distributed filarial parasite of dogs, is known to cause serious or fatal cardiopulmonary disease. Client-owned dogs were enrolled in a clinical field study in the USA to evaluate the clinical effectiveness and field safety of an orally administered combination investigational product (IP) containing milbemycin oxime and lotilaner (Credelio® Plus) as compared to a control product (CP) for the prevention of heartworm disease when administered monthly for 11 consecutive months. Methods In this 11-month field study, 319 dogs ≥ 8 weeks old confirmed to be heartworm-negative were enrolled from eight geographically distinct US veterinary clinics, including sites in the southern USA and Mississippi River Valley. The dogs were treated with either the IP combination product at 0.75–1.53 mg/kg milbemycin oxime and 20–41.5 mg/kg lotilaner (n = 159) or the CP (Sentinel® Flavor Tabs®; milbemycin oxime/lufenuron) at the label-recommended dose rate (n = 158.) On day 330, effectiveness was evaluated in each dog using antigen and microfilarial (modified Knott’s) testing to assess the establishment of any patent adult heartworm infections. Results All dogs treated with the IP combination product and the CP tested negative (100% prevention) for heartworm infection on day 330. The IP combination product tablets containing milbemycin oxime and lotilaner were well tolerated based on the safety assessments in all treated dogs. Conclusions This multi-site clinical study using client-owned dogs demonstrated that monthly use of flavored, chewable tablets containing a combination of milbemycin oxime and lotilaner administered orally under end use conditions is safe for dogs. None of the enrolled dogs developed heartworm infections. Eleven consecutive monthly treatments of the IP provided 100% prevention of heartworm disease caused by D. immitis. Graphic Abstract

scholarly journals Effectiveness of a novel orally administered combination drug product containing milbemycin oxime and lotilaner (Credelio® Plus) for the treatment of larval and immature adult stages of Ancylostoma caninum in experimentally infected dogs

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Daniel E. Snyder ◽  
Scott Wiseman ◽  
Elizabeth Crawley ◽  
Kim Wallace ◽  
Dwight D. Bowman ◽  
...  
Keyword(s):  
Drug Product ◽  
Geometric Mean ◽  
Time Frame ◽  
Immature Stage ◽  
Combination Drug ◽  
Ancylostoma Caninum ◽  
Combination Tablet ◽  
Milbemycin Oxime ◽  
Infective Larvae ◽  
Intestinal Nematode

Abstract Background The hookworm, Ancylostoma caninum, is a common and important zoonotic intestinal nematode parasite that infects dogs globally. Both the immature and adult stages of A. caninum ingest large volumes of blood during the feeding process and can cause severe anemia and death in young dogs, even before patent infections can be diagnosed using routine faecal examination methods. Thus, effective treatment of any pre-patent stages of immature hookworms can reduce or eliminate the risk of clinical disease in infected dogs and additionally reduce environmental contamination of eggs and infective larvae. Two randomized, blinded, GCP-compliant, pivotal laboratory dose confirmation studies were conducted to evaluate the effectiveness and safety of a new novel combination of lotilaner and milbemycin oxime tablets (Credelio Plus®) administered orally to dogs experimentally infected with immature (L4 and immature adult [L5]) stages of A. caninum. Methods Treatments using the intended global commercial tablet formulation of Credelio Plus were administered in a time frame relative to inoculation with infective larvae so that effectiveness could be assessed against each specific immature stage of A. caninum. In each study, dogs were randomized to one of six (study 1) or four (study 2) treatment groups. Each treatment group contained 8 (study 1) or 10 (study 2) dogs that had been experimentally inoculated with infective A. caninum larvae on day 0 and were dosed once on day 7 or day 11. Enrolled subjects were administered placebo tablets, Credelio Plus tablets, or lotilaner mono tablets to provide minimum dosages of 0.75 mg/kg of milbemycin oxime and 20 mg/kg of lotilaner. All dogs were necropsied 5 days after their respective treatment. All nematodes recovered from the gastrointestinal tract at necropsy were counted by species and stage. Results For both dose confirmation studies and based on geometric mean worm counts, efficacy of Credelio Plus was ≥ 97.3% against L4 larval stage of A. caninum and ≥ 98.7% against immature adult (L5) A. caninum. Conclusions These studies demonstrated that the orally administered Credelio Plus combination tablet was highly efficacious in treating immature (L4 and immature adult [L5]) stages of A. caninum in experimentally infected dogs.

scholarly journals Field study to investigate the effectiveness and safety of a novel orally administered combination drug product containing milbemycin oxime and lotilaner (Credelio® Plus) against natural flea and tick infestations on dogs presented as veterinary patients in Europe

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Sophie Forster ◽  
Scott Wiseman ◽  
Daniel E. Snyder
Keyword(s):  
Field Study ◽  
Treatment Time ◽  
Drug Product ◽  
Clinical Signs ◽  
Rhipicephalus Sanguineus ◽  
Time Frame ◽  
Combination Drug ◽  
Combination Tablet ◽  
Milbemycin Oxime ◽  
Pulex Irritans

Abstract Background A pivotal randomised, blinded, positive-controlled, multicentre, European field study was conducted to evaluate the effectiveness and safety of a novel combination tablet of lotilaner and milbemycin oxime (Credelio® Plus) administered orally to client-owned dogs naturally infested with fleas and/or ticks. Methods In this field study, households with flea- or tick-infested dog(s) were enrolled on Day 0 into the study to provide data for either the tick or flea infestation cohorts. Households were randomised in a 2:1 ratio to receive either the combination investigational product (IP, Credelio Plus® tablets) or the control product (CP: Nexgard Spectra® tablets). Dogs were administered IP (flea cohort n = 135; tick cohort: n = 147) or CP (flea cohort: n = 67; tick cohort: n = 74) once every 4 weeks for a total of three times at a dose rate of 20.0–41.5 mg/kg bodyweight lotilaner and 0.75–1.53 mg/kg bodyweight milbemycin oxime (IP) or as recommended (CP). Percentage reduction was calculated by comparing individual dog flea and tick counts at each assessed post-treatment time point to their respective baseline (pre-treatment) infestation. Resolution of the clinical signs of flea allergy dermatitis (FAD) was assessed in flea-allergic dogs on the days that flea counts were performed. Results Flea effectiveness of Credelio Plus® after 3 consecutive monthly treatments was 100% against Ctenocephalides felis, C. canis and Pulex irritans. Tick effectiveness of Credelio Plus® over the same time frame was 99.3% for Ixodes ricinus and 100% against Rhipicephalus sanguineus (s.l.). Flea effectiveness of the CP after three consecutive monthly treatments was 100% against C. felis, C. canis and P. irritans. Tick effectiveness of the CP over the same time frame was 99.8% for I. ricinus and 100% against R. sanguineus. Credelio Plus® was well tolerated based on the safety assessments in all treated dogs in this field study. Within both treatment groups there was a reduction in total FAD scores from baseline. Conclusions This pivotal European field study demonstrated the excellent effectiveness and safety of a combination of lotilaner and milbemycin oxime (Credelio Plus®) administered orally to dogs naturally infested with fleas and/or ticks. Graphic Abstract

scholarly journals Effectiveness of Credelio® Plus, a novel chewable tablet containing milbemycin oxime and lotilaner for the treatment of larval and immature adult stages of Toxocara canis in experimentally infected dogs

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Lisa M. Young ◽  
Scott Wiseman ◽  
Elizabeth Crawley ◽  
Dwight D. Bowman ◽  
Craig R. Reinemeyer ◽  
...  
Keyword(s):  
Geometric Mean ◽  
Toxocara Canis ◽  
Time Frame ◽  
Immature Stage ◽  
Chewable Tablet ◽  
Combination Tablet ◽  
Milbemycin Oxime ◽  
Treatment Groups ◽  
Intestinal Nematode ◽  
Respective Treatment

Abstract Background The ascarid, Toxocara canis, is a common and important zoonotic intestinal nematode parasite that infects dogs globally. An effective treatment that kills any pre-patent stages of immature T. canis could additionally reduce or eliminate the development of patent infections that can result in clinical disease in infected dogs and would further reduce environmental contamination of eggs. Two randomized, blinded, GCP-compliant, pivotal laboratory dose confirmation studies were conducted to assess the effectiveness and safety of a new novel combination of lotilaner and milbemycin oxime tablets (Credelio Plus) administered orally to dogs that were experimentally infected with immature (L4 or immature adult [L5]) stages of T. canis. Methods The commercial tablet formulation of Credelio Plus® was administered in a time frame relative to inoculation with infective eggs. This allowed for effectiveness to be assessed against each specific immature stage of T. canis. In each study, dogs were randomized and allocated to one of four treatment groups. Each treatment group contained ten dogs that had been experimentally inoculated on Day 0 with infective T. canis eggs and then were dosed once on Day 14 or Day 24 using either placebo tablets or Credelio Plus tablets (IP) to provide minimum dosages of 0.75 mg/kg of milbemycin oxime and 20 mg/kg of lotilaner. All dogs were necropsied 5 or 6 days after their respective treatment. At necropsy, all nematodes recovered from the gastrointestinal tract were counted by species and stage. Results In both dose confirmation studies using geometric mean worm counts, effectiveness of Credelio Plus was ≥ 98.6% and ≥ 96.8% against L4 larval stage T. canis and immature adult [L5] T. canis in both studies, respectively. Conclusions These studies demonstrated that the Credelio Plus combination tablet administered orally to dogs was highly efficacious against experimental infections with L4 and immature adult [L5] stages of T. canis.

New Drugs of 2012: A Concise Overview of the NMEs and Trends for Innovative Brand Market in the United States

2013 ◽  
Vol 6 (2) ◽  
pp. 2009-2013
Author(s):  
D Samba Reddy
Keyword(s):  
Drug Approval ◽  
The United States ◽  
New Drugs ◽  
New Combination ◽  
Drug Status ◽  
Combination Drug ◽  
Human Cord Blood ◽  
Life Saving ◽  
Genomics And Proteomics ◽  
The Face

Thirty-nine (39) new drugs have been approved by the U.S. FDA in 2012, a record highest number of approvals since 1996. The record is a sign that pharma companies are poised to tap recent advances from genomics and proteomics. This list includes novel new drugs, known as new molecular entities (NMEs), biologics and new products. Many life-saving drugs are approved for marketing. The list includes a total of 10 drugs for cancer treatment, and nearly a quarter of those approved in 2012 had orphan drug status.  Among the breakthrough drugs approved in 2012 were ivacaftor (cystic fibrosis), vasmodegib (skin cancer), HPC-C (human cord blood product), ruxolitinib (myelofibrosis) and a new combination drug to treat HIV. In addition,  several unique products were approved for the treatment of macular degeneration, chronic weight management, overactive bladder, actinic keratosis, erectile dysfunction, glaucoma, respiratory distress syndrome, and COPD. The approval of 39 drugs in 2012 underscores a robust success rate and confirms that innovation is once again beginning to pay off. In the existing climate of reduced revenues in the face of generic competitions, the future and survival of big companies rests heavily on their unique niche products. It is apparent that big Pharma and a growing number of emerging Biotechs alike have focused their attention on developing new NMEs for rare diseases. In 2012, the length of the FDA’s review is shorter than agencies in other countries. Innovative models adopted for R&D strategies, communications, and new regulatory changes appear to shorten development timelines. Despite record drug approvals, there is bleak scope for blockbusters because most of these drugs have a limited market. The pipeline for blockbusters appears very low. However, there is unmet medical need for new drugs in autism, Alzheimer’s disease and epilepsy. Overall, the new drug approval list unveils unique and reemerging trends indicating that the pharma companies are poised for big growth from new brands approved for marketing for narrow-spectrum indications.    

Bioequivalence of Dapagliflozin/Metformin Extended-release Fixed-combination Drug Product and Single-component Dapagliflozin and Metformin Extended-release Tablets in Healthy Russian Subjects

2018 ◽  
Vol 40 (4) ◽  
pp. 550-561.e3 ◽  
Author(s):  
Yunona Khomitskaya ◽  
Nadezhda Tikhonova ◽  
Konstantin Gudkov ◽  
Svetlana Erofeeva ◽  
Victoria Holmes ◽  
...  
Keyword(s):  
Extended Release ◽  
Fixed Combination ◽  
Drug Product ◽  
Single Component ◽  
Combination Drug

scholarly journals In VitroSynergistic Effect of Curcumin in Combination with Third Generation Cephalosporins against Bacteria Associated with Infectious Diarrhea

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Nishanth Kumar Sasidharan ◽  
Sreerag Ravikumar Sreekala ◽  
Jubi Jacob ◽  
Bala Nambisan
Keyword(s):  
Synergistic Effect ◽  
New Combination ◽  
Normal Fibroblast ◽  
Infectious Diarrhea ◽  
Combination Drug ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Time Kill ◽  
Third Generation Cephalosporins

Diarrhea is one of the leading causes of morbidity and mortality in humans in developed and developing countries. Furthermore, increased resistance to antibiotics has resulted in serious challenges in the treatment of this infectious disease worldwide. Therefore, there exists a need to develop alternative natural or combination drug therapies. The aim of the present study was to investigate the synergistic effect of curcumin-1 in combination with three antibiotics against five diarrhea causing bacteria. The antibacterial activity of curcumin-1 and antibiotics was assessed by the broth microdilution method, checkerboard dilution test, and time-kill assay. Antimicrobial activity of curcumin-1 was observed against all tested strains. The MICs of curcumin-1 against test bacteria ranged from 125 to 1000 μg/mL. In the checkerboard test, curcumin-1 markedly reduced the MICs of the antibiotics cefaclor, cefodizime, and cefotaxime. Significant synergistic effect was recorded by curcumin-1 in combination with cefotaxime. The toxicity of curcumin-1 with and without antibiotics was tested against foreskin (FS) normal fibroblast and no significant cytotoxicity was observed. From our result it is evident that curcumin-1 enhances the antibiotic potentials against diarrhea causing bacteria inin vitrocondition. This study suggested that curcumin-1 in combination with antibiotics could lead to the development of new combination of antibiotics against diarrhea causing bacteria.

scholarly journals A validated stability-indicating RP-HPLC method for paracetamol and lornoxicam: Application to pharmaceutical dosage forms

2014 ◽  
Vol 20 (1) ◽  
pp. 109-114
Author(s):  
Kulandaivelu Karunakaran ◽  
Gurusamy Navaneethan ◽  
Kuppanagounder Pitchaimuthu
Keyword(s):  
Drug Product ◽  
Potassium Dihydrogen Phosphate ◽  
Reversed Phase ◽  
Hplc Method ◽  
High Dose ◽  
Dihydrogen Phosphate ◽  
Combination Drug ◽  
Pharmaceutical Dosage Forms ◽  
Column Temperature ◽  
Stability Indicating

A new method for the simultaneous determination of paracetamol (PR) and lornoxicam (LR) has been developed by reversed phase HPLC from the combination drug product. The separation achieved on C18 column using acetonitrile and 0.02 M potassium dihydrogen phosphate was in the ratio of 35:65 (v/v) as mobile phase at a flow rate of 1.0 mL/min. Both the components were monitored at a single wavelength at 260 nm and the column temperature was maintained at 30?C throughout the analysis. A linear response was found in the concentration range of 125-375 ?g/mL for PR and 2-6 ?g/mL for LR, with the correlation coefficient of more than 0.999. Although the tablet contained a high dose of PR (500 mg) and a low dose of LR (8 mg), the single HPLC method was developed and the intra as well as inter day precision was obtained at less than 2% of RSD. The accuracy results obtained were between 98% and 102%. The drug was intentionally degraded under acidic, basic, peroxide, thermal, and photolytic conditions. The major degradation observed for both PR and LR under peroxide condition indicated that the drug product is susceptible to oxidation. The degraded peaks were properly resolved from PR and LR. Hence, the method is stability indicating.

Comparing irrigated biodynamic and conventionally managed dairy farms. 2. Milk production and composition and animal health

2007 ◽  
Vol 47 (5) ◽  
pp. 489 ◽  
Author(s):  
L. L. Burkitt ◽  
W. J. Wales ◽  
J. W. McDonald ◽  
D. R. Small ◽  
M. L. Jenkin
Keyword(s):  
Milk Production ◽  
Disease Incidence ◽  
Animal Health ◽  
Parasitic Infection ◽  
Cattle Breed ◽  
Dairy Farms ◽  
Experimental Period ◽  
Chemical Treatments ◽  
Cell Counts ◽  
Faecal Egg Counts

Ten paired irrigated dairy farms under biodynamic (BD) and conventional (CV) management were compared over a 3-year period (1991–93). The paired farms were located in the irrigation districts of northern Victoria and southern New South Wales and were matched for soil type, cattle breed and farm area. The BD farms practised BD principles for an average of 16 years before the study. The effects of farm management on milk yields and composition and animal health were examined by annually surveying farm managers regarding disease incidence and chemical treatment of animals, and by measuring milk yield and composition and faecal egg counts over the experimental period. The two hypotheses tested were that (1) milk volume and milk solids per cow would be lower under BD management, and (2) the incidence of internal parasitic infection and disease would be lower under CV management. Milk production and milk components produced, both on a per hectare and per cow basis, were 24–36% higher (P < 0.01) under CV management, due to significantly higher pasture intakes (P < 0.001). Although the incidence of parasitic infection was similar for mature cows, CV farms consistently used a greater number of chemical treatments (P < 0.05). Although BD heifer calves <8 months in age had significantly (P < 0.05) higher faecal egg counts, the results highlight the risk of reduced growth rates in calves due to high rates of parasite infection, under both management systems. Somatic cell counts were higher (P < 0.05) under BD management, with this being consistent with the use of significantly less chemical treatments under this management system. The implications of these findings for both CV and BD management for milk production and animal health are discussed.

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