A phase I pharmacokinetics trial comparing PF-05280014 (a potential biosimilar) and trastuzumab in healthy volunteers (REFLECTIONS B327-01).

2013 ◽  
Vol 31 (26_suppl) ◽  
pp. 171-171 ◽  
Author(s):  
Donghua Yin ◽  
Kerry B. Barker ◽  
Ruifeng Li ◽  
Xu Meng ◽  
Steven D. Reich ◽  
...  
Keyword(s):  
Double Blind Trial ◽  
Healthy Male ◽  
Double Blind ◽  
Treatment Interruptions ◽  
The Us ◽  
Identical Amino Acid Sequence ◽  
To Receive ◽  
Clinical Trial Information ◽  
Time Point

171 Background: PF-05280014, a proposed biosimilar to trastuzumab, has an identical amino acid sequence and similar physicochemical and in vitro functional properties to trastuzumab. This study was designed to demonstrate PK similarity of PF-05280014 to trastuzumab from the US (trastuzumab-US) and EU (trastuzumab-EU), and between the licensed drugs. Safety and immunogenicity were also evaluated. Methods: In this double-blind trial (NCT01603264), 105 healthy male volunteers, 18-55 years old were randomized 1:1:1 to receive a single 6 mg/kg IV dose of PF-05280014, trastuzumab-US or trastuzumab-EU. All subjects provided informed consent. PK, safety and immunogenicity assessments were conducted for 70 days. PK similarity for a given test-to-reference comparison was considered to be demonstrated if the 90% CI of the test-to-reference ratio of the AUC from time 0 to the last time point (AUCT) and maximum concentration (Cmax) were within 80% – 125%. Results: The baseline demographics for the 101 subjects evaluable for PK were similar among 3 treatment arms. The 3 study drugs exhibited similar characteristics of target-mediated disposition and similar PK parameters (Table). The 90% CI for the ratios of Cmax, AUCT, and AUC0-∞were within 80% – 125% for the comparisons of PF-05280014 to trastuzumab-EU or trastuzumab-US, and trastuzumab-EU to trastuzumab-US. Adverse events (AE) were similar for the 3 arms with treatment-related AEs reported by 71.4%, 68.6%, and 65.7% subjects in the PF-05280014, trastuzumab-EU and trastuzumab-US, respectively. No serious AEs were reported. Only 4 subjects had treatment interruptions; 2 discontinued. Only 1 subject (trastuzumab-EU) developed anti-drug antibodies after dosing. Conclusions: This study demonstrates PK similarity of PF-05280014 to both trastuzumab-US and trastuzumab-EU and of trastuzumab-EU to trastuzumab-US. The 3 study drugs also showed similar safety profiles. Clinical trial information: NCT01603264. [Table: see text]

A phase I pharmacokinetics trial comparing PF-05280014 (a potential biosimilar) and trastuzumab in healthy volunteers (REFLECTIONS B327-01).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 612-612
Author(s):  
Donghua Yin ◽  
Kerry B Barker ◽  
Ruifeng Li ◽  
Xu Meng ◽  
Steven D Reich ◽  
...  
Keyword(s):  
Double Blind Trial ◽  
Healthy Male ◽  
Double Blind ◽  
Treatment Interruptions ◽  
The Us ◽  
Identical Amino Acid Sequence ◽  
To Receive ◽  
Clinical Trial Information ◽  
Time Point

612 Background: PF-05280014, a proposed biosimilar to trastuzumab, has an identical amino acid sequence and similar physicochemical and in vitro functional properties to trastuzumab. This study was designed to demonstrate PK similarity of PF-05280014 to trastuzumab from the US (trastuzumab-US) and EU (trastuzumab-EU), and between the licensed drugs. Safety and immunogenicity were also evaluated. Methods: In this double-blind trial (NCT01603264), 105 healthy male volunteers, 18-55 years old were randomized 1:1:1 to receive a single 6 mg/kg IV dose of PF-05280014, trastuzumab-US or trastuzumab-EU. All subjects provided informed consent. PK, safety, and immunogenicity assessments were conducted for 70 days. PK similarity for a given test-to-reference comparison was considered to be demonstrated if the 90% CI of the test-to-reference ratio of the AUC from time 0 to the last time point (AUCT) and maximum concentration (Cmax) were within 80% – 125%. Results: The baseline demographics for the 101 subjects evaluable for PK were similar among 3 treatment arms. The 3 study drugs exhibited similar characteristics of target-mediated disposition and similar PK parameters (Table). The 90% CI for the ratios of Cmax, AUCT, and AUC0-∞were within 80% – 125% for the comparisons of PF-05280014 to trastuzumab-EU or trastuzumab-US, and trastuzumab-EU to trastuzumab-US. Adverse events (AE) were similar for the 3 arms with treatment-related AEs reported by 71.4%, 68.6%, and 65.7% subjects in the PF-05280014, trastuzumab-EU and trastuzumab-US, respectively. No serious AEs were reported. Only 4 subjects had treatment interruptions; 2 discontinued. Only 1 subject (trastuzumab-EU) developed anti-drug antibodies after dosing. Conclusions: This study demonstrates PK similarity of PF-05280014 to both trastuzumab-US and trastuzumab-EU and of trastuzumab-EU to trastuzumab-US. The three study drugs also showed similar safety profiles. Clinical trial information: NCT01603264. [Table: see text]

The Efficacy of Electroconvulsive Therapy in the Treatment of Schizophrenia

1987 ◽  
Vol 151 (2) ◽  
pp. 152-155 ◽  
Author(s):  
K. R. Abraham ◽  
P. Kulhara
Keyword(s):  
Electroconvulsive Therapy ◽  
Rating Scale ◽  
Double Blind Trial ◽  
Double Blind ◽  
Blind Trial ◽  
Brief Psychiatric Rating Scale ◽  
Psychiatric Rating ◽  
Psychiatric Rating Scale ◽  
To Receive

The efficacy of ECT was investigated in a double-blind trial. Twenty-two patients with schizophrenia received trifluoperazine and were randomly allocated to receive eight real or eight simulated ECTs. In the first eight weeks, the group receiving real ECTs showed significantly more improvement as measured on the Brief Psychiatric Rating Scale. However, the groups showed no significant differences from the twelfth week onwards. The superiority of real ECT was not confirmed at the end of six months.

scholarly journals Efficacy of a nasal spray containing Iota-Carrageenan in the prophylaxis of COVID-19 in hospital personnel dedicated to patients care with COVID-19 disease. A pragmatic multicenter, randomized, double-blind, placebo-controlled trial (CARR-COV-02)

2021 ◽  
Author(s):  
Juan Manuel Figueroa ◽  
Monica Lombardo ◽  
Ariel Dogliotti ◽  
Luis Flynn ◽  
Robert P. Giugliano ◽  
...  
Keyword(s):  
Placebo Group ◽  
Nasal Spray ◽  
Controlled Trial ◽  
Hospital Personnel ◽  
Culture Methods ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Significant Efficacy ◽  
To Receive

Background Iota-Carrageenan (I-C) is a sulfate polysaccharide synthesized by red algae, with demonstrated antiviral activity and clinical efficacy as nasal spray in the treatment of common cold. In vitro, I-C inhibits SARS-CoV-2 infection in cell culture. Methods This is a pragmatic multicenter, randomized, double-blind, placebo-controlled trial assessing the use of a nasal spray containing I-C in the prophylaxis of COVID-19 in hospital personnel dedicated to care of COVID-19 patients. Clinically healthy physicians, nurses, kinesiologists and others medical providers were assigned in a 1:1 ratio to receive four daily doses of I-C spray or placebo for 21 days. The primary end point was clinical COVID-19, as confirmed by reverse-transcriptase-polymerase-chain-reaction testing, over a period of 21 days. The trial is registered at ClinicalTrials.gov (NCT04521322). Findings A total of 394 individuals were randomly assigned to receive I-C or placebo. Both treatment groups had similar baseline characteristics. The incidence of COVID-19 was significantly lower in the I-C group compared to placebo (1.0% vs 5.0%) (Odds Ratio 0.19 (95% confidence interval 0.05 to 0.77; p= 0.03). Workday loss in placebo group compared to I-C were 1.6% days / person (95% CI, 1.0 to 2.2); p <0.0001 There were no differences in the incidence of adverse events across the two groups (17.3% in the I-C group and 15.2% in the placebo group, p= 0.5). Interpretation I-C showed significant efficacy in preventing SARS-CoV-2 infection in hospital personnel dedicated to care patients with COVID-19 disease.

Hop Bract Polyphenols Reduced Three-day Dental Plaque Regrowth

2007 ◽  
Vol 86 (9) ◽  
pp. 848-851 ◽  
Author(s):  
K. Shinada ◽  
M. Tagashira ◽  
H. Watanabe ◽  
P. Sopapornamorn ◽  
A. Kanayama ◽  
...  
Keyword(s):  
Clinical Study ◽  
Oral Hygiene ◽  
Dental Plaque ◽  
Mutans Streptococci ◽  
Healthy Male ◽  
Inhibitory Effects ◽  
Performance Score ◽  
Double Blind ◽  
The Mean

Previous research has shown the inhibitory effects of hop bract polyphenols (HBP) on cariogenic streptococci in vitro, but their effects in humans have not been investigated. This double-blind, crossover clinical study tested the hypothesis that HBP delivered in a mouthrinse suppresses plaque regrowth in humans. Twenty-nine healthy male volunteers had all plaque removed, and refrained from all oral hygiene for 3 days, except for rinsing with a mouthrinse containing 0.1% HBP or a placebo. The results showed that the mean amount of plaque assessed by the Patient Hygiene Performance score after the volunteers used the HBP mouthrinse was significantly less than that after they used the placebo (p < 0.001). The number of mutans streptococci in the plaque samples after volunteers used the HBP mouthrinse was significantly lower than that after they used the placebo (p < 0.05). These findings suggested that HBP, delivered in a mouthrinse, successfully reduced dental plaque regrowth in humans.

Influence of Warfarin on Symptoms of Fatigue: Findings of a Randomized Trial

2005 ◽  
Vol 39 (5) ◽  
pp. 840-842 ◽  
Author(s):  
Michael J Kovacs ◽  
Clive Kearon ◽  
Jim A Julian ◽  
James D Douketis ◽  
Christine Demers ◽  
...  
Keyword(s):  
Risk Factor ◽  
Venous Thromboembolism ◽  
Warfarin Therapy ◽  
Study Drug ◽  
Global Rating ◽  
Double Blind Trial ◽  
Short Term ◽  
Open Label ◽  
Double Blind ◽  
To Receive

BACKGROUND: Some patients develop fatigue while taking warfarin, but causality is uncertain. OBJECTIVE: To assess whether warfarin use is associated with fatigue. METHODS: This investigation was a substudy of a randomized double-blind trial in 13 outpatient thromboembolism clinics. Subjects who had received one month of open-label warfarin therapy for venous thromboembolism due to a transient risk factor were randomly assigned to receive warfarin or placebo for 2 months and followed for another 9 months after stopping the study drug. Fatigue was measured using a Likert scale, and change of fatigue was measured by the patient's global rating. RESULTS: In 87 subjects, the overall ratings of fatigue were 0.1 unit lower (95% CI 0.6 units lower to 0.4 units higher) while taking warfarin. Global rating for change in fatigue intensity showed no increase of fatigue with warfarin use. CONCLUSIONS: The short-term use of warfarin was not associated with symptoms of fatigue.

A Multicentre Double Blind Trial of Fluoxetine versus Amitriptyline in the Treatment of Depressive Illness

1993 ◽  
Vol 27 (1) ◽  
pp. 49-55 ◽  
Author(s):  
Fiona K. Judd ◽  
Kate Moore ◽  
Trevor R. Norman ◽  
Graham D. Burrows ◽  
Ramesh K. Gupta ◽  
...  
Keyword(s):  
Side Effects ◽  
Side Effect ◽  
Serotonin Reuptake ◽  
Depressive Illness ◽  
Fixed Dose ◽  
Side Effect Profile ◽  
Double Blind Trial ◽  
Double Blind ◽  
Antidepressant Efficacy ◽  
To Receive

The antidepressant efficacy and side effect profile of a fixed dose of 20 mg/day of fluoxetine, a specific serotonin reuptake inhibitor, were compared to those of amitriptyline. Fifty-eight patients with DSM-III-R depression were randomly assigned to receive either fluoxetine or amitriptyline. Fifty-six patients (fluoxetine N = 23, amitriptyline N = 23) completed the 6 week study. Comparable antidepressant efficacy was demonstrated for the two drugs. Patients taking fluoxetine reported less side-effects than those taking amitriptyline.

Randomized Double-Blind Trial of Prophylactic Oral Minocycline and Topical Tazarotene for Cetuximab-Associated Acne-Like Eruption

2007 ◽  
Vol 25 (34) ◽  
pp. 5390-5396 ◽  
Author(s):  
Alon Scope ◽  
Anna Liza C. Agero ◽  
Stephen W. Dusza ◽  
Patricia L. Myskowski ◽  
Jocelyn A. Lieb ◽  
...  
Keyword(s):  
Lower Proportion ◽  
Double Blind Trial ◽  
Double Blind ◽  
Acneiform Rash ◽  
The Face ◽  
Grade 3 ◽  
Colorectal Cancer Patients ◽  
To Receive ◽  
Severe Rash ◽  
Cetuximab Therapy

Purpose To evaluate the ability of either oral minocycline, topical tazarotene or both, to reduce or prevent cetuximab-related acneiform rash when administered starting on day 1 of cetuximab therapy. Patients and Methods Metastatic colorectal cancer patients preparing to initiate cetuximab were randomly assigned to receive daily oral minocycline or placebo, and to receive topical tazarotene application to either left or right side of the face. Both therapies were administered for 8 weeks. Results Forty-eight eligible patients were randomly assigned to minocycline (n = 24) or placebo (n = 24). Total facial lesion counts were significantly lower in patients receiving minocycline at weeks 1 through 4. At week 4, a lower proportion of patients in the minocycline arm reported moderate to severe itch than in the placebo arm (20% v 50%, P = .05). Facial photographs, obtained at week 4, were reviewed for rash global severity. Patients in the minocycline arm trended toward lower frequency of moderate to severe rash than patients receiving placebo (20% v 42%, P = .13). The differences in total facial lesion counts and subjectively assessed itch were diminished by week 8. Cetuximab treatment was interrupted because of grade 3 skin rash in four patients in the placebo arm, and none in the minocycline arm. There was no observed clinical benefit to tazarotene application. Tazarotene treatment was associated with significant irritation, causing its discontinuation in one third of patients. Conclusion Prophylaxis with oral minocycline may be useful in decreasing the severity of the acneiform rash during the first month of cetuximab treatment. Topical tazarotene is not recommended for management of cetuximab-related rash.

Does biomarker information impact patients’ preferences for therapy?

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6527-6527
Author(s):  
Ann H. Partridge ◽  
Karen Sepucha ◽  
Anne O'Neill ◽  
Kathy Miller ◽  
Emily Baker ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Treatment Preference ◽  
Treatment Preferences ◽  
Double Blind Trial ◽  
Double Blind ◽  
Increased Risk ◽  
The Impact ◽  
To Receive

6527 Background: Biomarker information can risk stratify patients based on potential for benefits/toxicity from therapy. Ideally, a biomarker will identify those who benefit with limited toxicity. However, the impact of biomarkers is unclear when indicting individuals with greatest benefit are also at increased risk for toxicity. Methods: We surveyed participants at 18 month follow-up in the Decision-Making/Quality of Life (DM-QOL) component of ECOG5103, a RCT where patients were randomized to receive adjuvant chemotherapy for breast cancer with either placebo or bevacizumab (in 2 schedules). We asked patients for the preferred treatment in two hypothetical scenarios: 1) preference for chemo A or chemo A + B without biomarker information; 2) preference for chemo A or chemo A+B when participants tested positive for a “B-receptor” which increased both the benefit and toxicity of chemo A+B. McNemar’s test was used to examine changes in preferences. Results: 439 patients completed both scenarios on 18-month survey. The Table shows the treatment preferences in each scenario. The positive biomarker information in scenario 2 led 60/439 (14%) participants to switch their preference. The main reason for treatment preference in scenario 2 was greater benefits of chemo A+B (64%), the lower risks with chemo A (20%) and positive biomarker (10%). Among participants who changed preference, those randomized to receive bevacizumab were more likely to switch to chemo A in scenario 2. Conclusions: Information about a positive biomarker, indicating increased benefit and increased risk from additional chemo, did not significantly change participants’ preferred treatment. All participants were involved in a large placebo controlled double blind trial and the majority (70%) preferred the most aggressive course of treatment in both scenarios. Whether patients not enrolled in the trial would be more sensitive to the increased risk information is unclear. [Table: see text]

Sign in / Sign up

Export Citation Format

Share Document