Trial Outcomes & Findings for Arasertaconazole Nitrate Pessaries - Dose Finding Study for the Vulvovaginal Candidiasis (VVC) Treatment (NCT NCT01144286)

Last Updated: 2013-10-09

Results Overview

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".

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

229 participants

Primary outcome timeframe

day 26 ± 4 days

Results posted on

2013-10-09

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Placebo placebo pessary, single dose	Arasertaconazole Nitrate 150 mg Arasertaconazole nitrate 150 mg pessary, single dose	Arasertaconazole Nitrate 300 mg Arasertaconazole nitrate 300 mg pessary, single dose	Arasertaconazole 600 mg Arasertaconazole nitrate 600 mg pessary, single dose
Overall Study STARTED	57	58	58	56
Overall Study COMPLETED	57	58	58	56
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=57 Participants placebo pessary, single dose	Arasertaconazole Nitrate 150 mg n=58 Participants Arasertaconazole nitrate 150 mg pessary, single dose	Arasertaconazole Nitrate 300 mg n=58 Participants Arasertaconazole nitrate 300 mg pessary, single dose	Arasertaconazole 600 mg n=56 Participants Arasertaconazole nitrate 600 mg pessary, single dose	Total n=229 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	57 Participants n=5 Participants	58 Participants n=7 Participants	58 Participants n=5 Participants	56 Participants n=4 Participants	229 Participants n=21 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age Continuous	30.1 years STANDARD_DEVIATION 7.74 • n=5 Participants	32.8 years STANDARD_DEVIATION 8.47 • n=7 Participants	29.7 years STANDARD_DEVIATION 7.58 • n=5 Participants	31.8 years STANDARD_DEVIATION 8.53 • n=4 Participants	31.1 years STANDARD_DEVIATION 8.13 • n=21 Participants
Sex: Female, Male Female	57 Participants n=5 Participants	58 Participants n=7 Participants	58 Participants n=5 Participants	56 Participants n=4 Participants	229 Participants n=21 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Region of Enrollment Europe	57 participants n=5 Participants	58 participants n=7 Participants	58 participants n=5 Participants	56 participants n=4 Participants	229 participants n=21 Participants

PRIMARY outcome

Timeframe: day 26 ± 4 days

Population: 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.

Outcome measures

Outcome measures
Measure	Placebo n=57 Participants placebo pessary, single dose	Arasertaconazole Nitrate 150 mg n=58 Participants Arasertaconazole nitrate 150 mg pessary, single dose	Arasertaconazole Nitrate 300 mg n=58 Participants Arasertaconazole nitrate 300 mg pessary, single dose	Arasertaconazole 600 mg n=56 Participants Arasertaconazole nitrate 600 mg pessary, single dose
Dose-response of Clinical and Mycological (Global) Therapeutic Response	31.7 percentage of patients cured Interval 18.08 to 48.09	48.7 percentage of patients cured Interval 32.42 to 65.22	47.6 percentage of patients cured Interval 32.0 to 63.58	53.8 percentage of patients cured Interval 37.18 to 69.91

SECONDARY outcome

Timeframe: Day 8 ± 2 days

Population: 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.

Global therapeutic response at day 8± 2 days. Safety and tolerability.

Outcome measures

Outcome measures
Measure	Placebo n=57 Participants placebo pessary, single dose	Arasertaconazole Nitrate 150 mg n=58 Participants Arasertaconazole nitrate 150 mg pessary, single dose	Arasertaconazole Nitrate 300 mg n=58 Participants Arasertaconazole nitrate 300 mg pessary, single dose	Arasertaconazole 600 mg n=56 Participants Arasertaconazole nitrate 600 mg pessary, single dose
Dose-response of Clinical and Mycological (Global)Therapeutic Response	15.6 percentage of cured participants Interval 6.49 to 29.46	34.2 percentage of cured participants Interval 19.63 to 51.35	46.3 percentage of cured participants Interval 30.66 to 62.58	61.0 percentage of cured participants Interval 44.5 to 75.8

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Arasertaconazole Nitrate 150 mg

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Arasertaconazole Nitrate 300 mg

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Arasertaconazole 600 mg

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Vladimir Dvorak

Privatni gynekologicka ambulance

Phone: +420 542 221 661

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=57 participants at risk placebo pessary, single dose	Arasertaconazole Nitrate 150 mg n=58 participants at risk Arasertaconazole nitrate 150 mg pessary, single dose	Arasertaconazole Nitrate 300 mg n=58 participants at risk Arasertaconazole nitrate 300 mg pessary, single dose	Arasertaconazole 600 mg n=56 participants at risk Arasertaconazole nitrate 600 mg pessary, single dose
Respiratory, thoracic and mediastinal disorders rhinitis allergic	0.00% 0/57 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/58 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/58 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	1.8% 1/56 • Number of events 1 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010
Respiratory, thoracic and mediastinal disorders oropharyngeal pain	0.00% 0/57 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/58 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/58 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	1.8% 1/56 • Number of events 1 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010
Infections and infestations tonsilitis	1.8% 1/57 • Number of events 1 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/58 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/58 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/56 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010
Infections and infestations Chamydial infection	1.8% 1/57 • Number of events 1 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/58 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/58 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/56 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010
Injury, poisoning and procedural complications heat stroke	1.8% 1/57 • Number of events 1 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/58 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/58 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/56 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010
Nervous system disorders headache	1.8% 1/57 • Number of events 1 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	3.4% 2/58 • Number of events 2 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	5.2% 3/58 • Number of events 3 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	3.6% 2/56 • Number of events 2 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010
Reproductive system and breast disorders vulvovaginal burning sensation	1.8% 1/57 • Number of events 1 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/58 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/58 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	1.8% 1/56 • Number of events 1 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010
Skin and subcutaneous tissue disorders pruritus	1.8% 1/57 • Number of events 1 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	1.7% 1/58 • Number of events 1 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/58 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/56 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010
Gastrointestinal disorders abdominal distension	0.00% 0/57 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	1.7% 1/58 • Number of events 1 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/58 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/56 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010
Infections and infestations vaginal infection	0.00% 0/57 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	1.7% 1/58 • Number of events 1 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/58 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/56 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010
Infections and infestations nasopharyngitis	0.00% 0/57 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	1.7% 1/58 • Number of events 1 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/58 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/56 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010
Infections and infestations respiratory tract infection	0.00% 0/57 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	1.7% 1/58 • Number of events 1 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/58 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/56 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010
Infections and infestations rhinitis	0.00% 0/57 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	1.7% 1/58 • Number of events 1 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/58 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/56 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010
Musculoskeletal and connective tissue disorders pain in extremity	0.00% 0/57 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	1.7% 1/58 • Number of events 1 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	1.7% 1/58 • Number of events 1 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/56 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010
Cardiac disorders arrhythmia	0.00% 0/57 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/58 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	1.7% 1/58 • Number of events 3 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/56 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010
Ear and labyrinth disorders vertigo	0.00% 0/57 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/58 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	1.7% 1/58 • Number of events 1 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/56 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010
General disorders bloody discharge	0.00% 0/57 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/58 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	1.7% 1/58 • Number of events 1 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/56 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010
Infections and infestations influenza	0.00% 0/57 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/58 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	3.4% 2/58 • Number of events 2 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/56 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010
Investigations electrocardiogram TWave decreased	0.00% 0/57 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/58 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	1.7% 1/58 • Number of events 1 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/56 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010
Pregnancy, puerperium and perinatal conditions pregnancy	0.00% 0/57 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/58 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	1.7% 1/58 • Number of events 1 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	1.8% 1/56 • Number of events 1 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010
Reproductive system and breast disorders vulvovaginal discomfort	0.00% 0/57 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/58 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	1.7% 1/58 • Number of events 1 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/56 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010
Reproductive system and breast disorders dyspareunia	0.00% 0/57 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/58 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	1.7% 1/58 • Number of events 1 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/56 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010
Gastrointestinal disorders nausea	0.00% 0/57 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/58 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/58 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	1.8% 1/56 • Number of events 1 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010
Infections and infestations vaginitis bacterial	0.00% 0/57 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/58 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/58 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	1.8% 1/56 • Number of events 1 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010
Investigations blood bilirrubin increased	0.00% 0/57 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/58 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/58 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	1.8% 1/56 • Number of events 1 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010
Nervous system disorders migraine	0.00% 0/57 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/58 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/58 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	1.8% 1/56 • Number of events 1 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010
Renal and urinary disorders urinary incontinence	0.00% 0/57 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/58 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/58 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	1.8% 1/56 • Number of events 1 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010
Reproductive system and breast disorders pelvic pain	0.00% 0/57 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/58 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/58 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	1.8% 1/56 • Number of events 1 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010
Reproductive system and breast disorders uterine haemorrhage	0.00% 0/57 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/58 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	0.00% 0/58 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010	1.8% 1/56 • Number of events 2 • Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010