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Arasertaconazole Nitrate Pessaries - Dose Finding Study for the Vulvovaginal Candidiasis (VVC) Treatment

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ClinicalTrials.gov Identifier: NCT01144286
Recruitment Status : Completed
First Posted : June 15, 2010
Results First Posted : October 9, 2013
Last Update Posted : October 9, 2013
Sponsor:
Information provided by (Responsible Party):
Ferrer Internacional S.A.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Vulvovaginal Candidiasis
Interventions Drug: arasertaconazole nitrate
Drug: placebo
Enrollment 229
Recruitment Details The subjects were randomized to a treatment arm using an interactive web response system (IWRS). Placebo and study drug pessaries were dispensed as a kit, and all subjects were instructed in proper self-administration of the pessaries (at bedtime while lying down). Study initiation date was 15June2010 and completed on 15 Nov 2010.
Pre-assignment Details After signed informed consent, VVC clinical signs and symptoms were assessed,(KOH) wet mounts and samples for mycological culture obtained.Baseline safety assessments, including pregnancy were performed. If all inclusion criteria and none of the exclusion criteria were met, the subject was randomized in the same day to one of the treatment groups.
Arm/Group Title Placebo Arasertaconazole Nitrate 150 mg Arasertaconazole Nitrate 300 mg Arasertaconazole 600 mg
Hide Arm/Group Description placebo pessary, single dose Arasertaconazole nitrate 150 mg pessary, single dose Arasertaconazole nitrate 300 mg pessary, single dose Arasertaconazole nitrate 600 mg pessary, single dose
Period Title: Overall Study
Started 57 58 58 56
Completed 57 58 58 56
Not Completed 0 0 0 0
Arm/Group Title Placebo Arasertaconazole Nitrate 150 mg Arasertaconazole Nitrate 300 mg Arasertaconazole 600 mg Total
Hide Arm/Group Description placebo pessary, single dose Arasertaconazole nitrate 150 mg pessary, single dose Arasertaconazole nitrate 300 mg pessary, single dose Arasertaconazole nitrate 600 mg pessary, single dose Total of all reporting groups
Overall Number of Baseline Participants 57 58 58 56 229
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 57 participants 58 participants 58 participants 56 participants 229 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
57
 100.0%
58
 100.0%
58
 100.0%
56
 100.0%
229
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 57 participants 58 participants 58 participants 56 participants 229 participants
30.1  (7.74) 32.8  (8.47) 29.7  (7.58) 31.8  (8.53) 31.1  (8.13)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 57 participants 58 participants 58 participants 56 participants 229 participants
Female
57
 100.0%
58
 100.0%
58
 100.0%
56
 100.0%
229
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Europe Number Analyzed 57 participants 58 participants 58 participants 56 participants 229 participants
57 58 58 56 229
1.Primary Outcome
Title Dose-response of Clinical and Mycological (Global) Therapeutic Response
Hide Description Global therapeutic response at day 26± 4 days ("TOC"- Test-of-Cure visit).Global therapeutic response is a composite endpoint using the clinical (signs and symptoms) and the mycological cures (microbiological culture), according to FDA guideline "Vulvovaginal Candidiasis —Developing Antimicrobial Drugs for Treatment".
Time Frame day 26 ± 4 days
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) was the primary population for the analysis of all efficacy endpoints. The FAS was defined as all randomized subjects who received at least 1 dose of a study drug.Subjects in the FAS were analyzed according to randomized treatment group.
Arm/Group Title Placebo Arasertaconazole Nitrate 150 mg Arasertaconazole Nitrate 300 mg Arasertaconazole 600 mg
Hide Arm/Group Description:
placebo pessary, single dose
Arasertaconazole nitrate 150 mg pessary, single dose
Arasertaconazole nitrate 300 mg pessary, single dose
Arasertaconazole nitrate 600 mg pessary, single dose
Overall Number of Participants Analyzed 57 58 58 56
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of patients cured
31.7
(18.08 to 48.09)
48.7
(32.42 to 65.22)
47.6
(32.00 to 63.58)
53.8
(37.18 to 69.91)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Arasertaconazole Nitrate 150 mg, Arasertaconazole Nitrate 300 mg, Arasertaconazole 600 mg
Comments

Primary analysis is the dose response at TOC based on the global therapeutic cure. Dose response will be tested using a logistic regression using linear coefficient for the treatment effect(Wald chi-square).

Assuming that the response rate is 80% for 600 mg, 75% for the 300 mg, 65% for 150 mg and 50% for the placebo group, a sample size of 45 subjects in each group will have 90% power to detect a linear dose response using a 0.05 two-sided test of trend based on the logistic model.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0630
Comments Significance level was set to α of 0.05 if the primary endpoint was significant, hierarchical testing was to be performed on the primary endpoint (each active dose X placebo). No other adjustment was made for testing multiple secondary outcomes.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter response rate (%)
Estimated Value 80
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Dose-response of Clinical and Mycological (Global)Therapeutic Response
Hide Description Global therapeutic response at day 8± 2 days. Safety and tolerability.
Time Frame Day 8 ± 2 days
Hide Outcome Measure Data
Hide Analysis Population Description
Dose response tested using logistic regression-linear coefficient for treatment effect.Assuming response rate 80% for 600 mg, 75% for 300 mg, 65% for 150 mg and 50% for the placebo group, sample size of 45 subjects in each group have 90% power to detect linear dose response with 0.05 two-sided test of trend based on the logistic model.
Arm/Group Title Placebo Arasertaconazole Nitrate 150 mg Arasertaconazole Nitrate 300 mg Arasertaconazole 600 mg
Hide Arm/Group Description:
placebo pessary, single dose
Arasertaconazole nitrate 150 mg pessary, single dose
Arasertaconazole nitrate 300 mg pessary, single dose
Arasertaconazole nitrate 600 mg pessary, single dose
Overall Number of Participants Analyzed 57 58 58 56
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of cured participants
15.6
(6.49 to 29.46)
34.2
(19.63 to 51.35)
46.3
(30.66 to 62.58)
61.0
(44.50 to 75.80)
Time Frame Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo Arasertaconazole Nitrate 150 mg Arasertaconazole Nitrate 300 mg Arasertaconazole 600 mg
Hide Arm/Group Description placebo pessary, single dose Arasertaconazole nitrate 150 mg pessary, single dose Arasertaconazole nitrate 300 mg pessary, single dose Arasertaconazole nitrate 600 mg pessary, single dose
All-Cause Mortality
Placebo Arasertaconazole Nitrate 150 mg Arasertaconazole Nitrate 300 mg Arasertaconazole 600 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Arasertaconazole Nitrate 150 mg Arasertaconazole Nitrate 300 mg Arasertaconazole 600 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/57 (0.00%)      0/58 (0.00%)      0/58 (0.00%)      0/56 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Placebo Arasertaconazole Nitrate 150 mg Arasertaconazole Nitrate 300 mg Arasertaconazole 600 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/57 (10.53%)      9/58 (15.52%)      13/58 (22.41%)      13/56 (23.21%)    
Cardiac disorders         
arrhythmia  1 [1]  0/57 (0.00%)  0 0/58 (0.00%)  0 1/58 (1.72%)  3 0/56 (0.00%)  0
Ear and labyrinth disorders         
vertigo  1 [1]  0/57 (0.00%)  0 0/58 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Gastrointestinal disorders         
abdominal distension  1 [2]  0/57 (0.00%)  0 1/58 (1.72%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
nausea  1 [3]  0/57 (0.00%)  0 0/58 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
General disorders         
bloody discharge  1 [2]  0/57 (0.00%)  0 0/58 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Infections and infestations         
tonsilitis  1 [4]  1/57 (1.75%)  1 0/58 (0.00%)  0 0/58 (0.00%)  0 0/56 (0.00%)  0
Chamydial infection  1 [5]  1/57 (1.75%)  1 0/58 (0.00%)  0 0/58 (0.00%)  0 0/56 (0.00%)  0
vaginal infection  1 [3]  0/57 (0.00%)  0 1/58 (1.72%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
nasopharyngitis  1 [3]  0/57 (0.00%)  0 1/58 (1.72%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
respiratory tract infection  1 [3]  0/57 (0.00%)  0 1/58 (1.72%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
rhinitis  1 [3]  0/57 (0.00%)  0 1/58 (1.72%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
influenza  1 [6]  0/57 (0.00%)  0 0/58 (0.00%)  0 2/58 (3.45%)  2 0/56 (0.00%)  0
vaginitis bacterial  1 [3]  0/57 (0.00%)  0 0/58 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Injury, poisoning and procedural complications         
heat stroke  1 [3]  1/57 (1.75%)  1 0/58 (0.00%)  0 0/58 (0.00%)  0 0/56 (0.00%)  0
Investigations         
electrocardiogram TWave decreased  1 [7]  0/57 (0.00%)  0 0/58 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
blood bilirrubin increased  1 [8]  0/57 (0.00%)  0 0/58 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Musculoskeletal and connective tissue disorders         
pain in extremity  1 [9]  0/57 (0.00%)  0 1/58 (1.72%)  1 1/58 (1.72%)  1 0/56 (0.00%)  0
Nervous system disorders         
headache  1 [3]  1/57 (1.75%)  1 2/58 (3.45%)  2 3/58 (5.17%)  3 2/56 (3.57%)  2
migraine  1 [3]  0/57 (0.00%)  0 0/58 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Pregnancy, puerperium and perinatal conditions         
pregnancy  1 [10]  0/57 (0.00%)  0 0/58 (0.00%)  0 1/58 (1.72%)  1 1/56 (1.79%)  1
Renal and urinary disorders         
urinary incontinence  1 [11]  0/57 (0.00%)  0 0/58 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Reproductive system and breast disorders         
vulvovaginal burning sensation  1 [2]  1/57 (1.75%)  1 0/58 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
vulvovaginal discomfort  1 [12]  0/57 (0.00%)  0 0/58 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
dyspareunia  1 [13]  0/57 (0.00%)  0 0/58 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
pelvic pain  1 [13]  0/57 (0.00%)  0 0/58 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
uterine haemorrhage  1 [2]  0/57 (0.00%)  0 0/58 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  2
Respiratory, thoracic and mediastinal disorders         
oropharyngeal pain  1 [3]  0/57 (0.00%)  0 0/58 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
rhinitis allergic  1 [3]  0/57 (0.00%)  0 0/58 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Skin and subcutaneous tissue disorders         
pruritus  1 [3]  1/57 (1.75%)  1 1/58 (1.72%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (13.0)
[1]
mild, unlikely, recovered
[2]
mild, possible related, recovered
[3]
mild, not related, recovered
[4]
moderate, not related,recovered
[5]
mild, not related, recovering
[6]
mild-moderate, not related, recovered
[7]
moderate, not assessable, recovered
[8]
mild, not related, not recovered
[9]
moderate, unlikely, recovered
[10]
There were 2 pregnancy cases. Patient exposed to 600 mg Arasertaconazole delivered healthy boy at 38th week gestation. Investigator last report received patient exposed to 300 mg Arasertaconazole: Ultrasound at 20th week of gestation was normal.
[11]
moderate, possible related, recovered
[12]
severe, probable related, recovered
[13]
moderate, not related, recovered
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The only disclosure restriction on the PI is that the sponsor can review publications and/or presentations (results communications) prior to public release and communications regarding trial results for a period that is 60 days from the time submitted to the sponsor for review. The sponsor may require changes to the publication and /or presentation regarding its content or the time of release.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Vladimir Dvorak
Organization: Privatni gynekologicka ambulance
Phone: +420 542 221 661
EMail: ssgcr@ti.cz
Layout table for additonal information
Responsible Party: Ferrer Internacional S.A.
ClinicalTrials.gov Identifier: NCT01144286     History of Changes
Other Study ID Numbers: P-090756-01
2009-016655-21 ( EudraCT Number )
First Submitted: June 9, 2010
First Posted: June 15, 2010
Results First Submitted: May 8, 2013
Results First Posted: October 9, 2013
Last Update Posted: October 9, 2013