Efficacy and Safety, Long-Term Study of NPC-01 to Treat Dysmenorrhea Associated With Endometriosis

• Sponsor: Nobelpharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00902746
• Collaborator: (none)
• Enrollment: 149
• Arm: 1
• Duration (Months): 33.1

Study Details

Study Description

Brief Summary

The purpose of this long-term study is to determine whether NPC-01 is effective in the treatment of dysmenorrhea associated with endometriosis.

Condition or Disease	Intervention/Treatment	Phase
Dysmenorrhea	Drug: NPC-01	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 149 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase3, Open-Label, Long-Term, NSAID-Add-on, Clinical Trial of NPC-01 for Treatment of Dysmenorrhea Associated With Endometriosis.
• Study Start Date: May 1, 2009
• Actual Primary Completion Date: Feb 1, 2012
• Actual Study Completion Date: Feb 1, 2012

Arms and Interventions

Arm

Intervention/Treatment

Experimental: NPC-01 Norethisterone, Ethinyl Estradiol

Drug: NPC-01; This study consist of the following steps. Step 1(Norethisterone 0.6mg, Ethinyl Estradiol 0.035mg):From first study medication to 3th menstrual cycles. Step 2(Norethisterone 1mg, Ethinyl Estradiol 0.035mg): After interim analysis of the results of step 1, in the case of the efficacy results meet prespecified criterion, same dose level will be continued to 13th menstrual cycles including step 1. If the results do not meet prespecified criterion, the dose will be increased to Norethisterone 1mg, Ethinyl Estradiol 0.035mg and be continued newly until 13th menstrual cycle from this point.

Outcome Measures

Primary Outcome Measures

1. Patient Response to Treatment for Dysmenorrhea, as Evaluated by Difference of Total Dysmenorrhea Score (Baseline/Pretreatment-End of Treatment) [52 weeks]

   The detail of dysmenorrhea score that was used in this study is the following. These subscales summed for a total dysmenorrhea score (minimum 0 to maximum 6). Pain score None 0 : None Mild 1 : There are some troubles for work Moderate 2 : Needing to rest in bed and/or affecting work Severe 3 : Morre than 1 day in bed and not possible to work Drug score (during a menstrual period) None 0 : None Mild 1 : taking analgesics for 1 days Moderate 2 : taking analgesics for 2 days Severe 3 : taking analgesics more than 3 days

Secondary Outcome Measures

1. Difference in the Visual Analog Scale (VAS) of Dysmenorrhea (Baseline/Pretreatment-dnd of Treatment) [52 weeks]

   VAS stands for Visual Analogue Scale of pain. The scale was rated as a graphic rating scale. as a 100mm baseline from 0:No pain to 100:Worst possible pain.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Dysmenorrhea associated with endometriosis

Exclusion Criteria:

• Severe hepatopathy

• Pregnant woman

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Nobelpharma

Investigators

• Study Director: Naoki Terakawa, M.D.,Ph.D., Nissay Hospital,Osaka,Japan

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Nobelpharma
• ClinicalTrials.gov Identifier: NCT00902746
• Other Study ID Numbers: NPC-01-1
• First Posted: May 15, 2009
• Last Update Posted: Jun 13, 2014
• Last Verified: May 1, 2014

• Additional relevant MeSH terms: Endometriosis; Dysmenorrhea

Study Results

Participant Flow

Recruitment Details	Total 168 patients were consented and registered at minus 2 cycles of study drug administration as provisional registration. After provisional registration, investigators confirmed their eligibility of patients by test gynecological examination, transvaginal ultrasound etc.) and 149 patients were formally registered for this study.

Arm/Group Title	NPC-01
Arm/Group Description	Norethisterone, Ethinyl Estradiol NPC-01: This study consist of the following steps. Step 1(Norethisterone 0.6mg, Ethinyl Estradiol 0.035mg):From first study medication to 3th menstrual cycles. Step 2(Norethisterone 1mg, Ethinyl Estradiol 0.035mg): After interim analysis of the results of step 1, in the case of the efficacy results meet prespecified criterion, same dose level will be continued to 13th menstrual cycles including step 1. If the results do not meet prespecified criterion, the dose will be increased to Norethisterone 1mg, Ethinyl Estradiol 0.035mg and be continued newly until 13th menstrual cycle from this point.
Period Title: Overall Study
STARTED	149
Initiation of Study Drug Administration	148
Transfer to Step 2	133
COMPLETED	113
NOT COMPLETED	36

Baseline Characteristics

Arm/Group Title	NPC-01
Arm/Group Description	Norethisterone, Ethinyl Estradiol NPC-01: This study consist of the following steps. Step 1(Norethisterone 0.6mg, Ethinyl Estradiol 0.035mg):From first study medication to 3th menstrual cycles. Step 2(Norethisterone 0.6mg, Ethinyl Estradiol 0.035mg, or Norethisterone 1mg, Ethinyl Estradiol 0.035mg): After interim analysis of the results of step 1, in the case of the efficacy results meet prespecified criterion, same dose level will be continued to 13th menstrual cycles including step 1. If the results do not meet prespecified criterion, the dose will be increased to Norethisterone 1mg, Ethinyl Estradiol 0.035mg and be continued newly until 13th menstrual cycle from this point.
Overall Participants	147
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	33.2 (7.12)
Age, Customized (participants) [Number]
Under 30 years of age	51 34.7%
30 year of age and older	96 65.3%
Sex/Gender, Customized (participants) [Number]
Female	147 100%
Total Dysmenorrhea Score (VRS; Verbal Rating Scale) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	4.1 (0.99)
Visual Analogue Scale (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	53.1 (21.49)

Outcome Measures

1. Primary Outcome

Title	Patient Response to Treatment for Dysmenorrhea, as Evaluated by Difference of Total Dysmenorrhea Score (Baseline/Pretreatment-End of Treatment)
Description	The detail of dysmenorrhea score that was used in this study is the following. These subscales summed for a total dysmenorrhea score (minimum 0 to maximum 6). Pain score None 0 : None Mild 1 : There are some troubles for work Moderate 2 : Needing to rest in bed and/or affecting work Severe 3 : Morre than 1 day in bed and not possible to work Drug score (during a menstrual period) None 0 : None Mild 1 : taking analgesics for 1 days Moderate 2 : taking analgesics for 2 days Severe 3 : taking analgesics more than 3 days
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

This analysis was carried out for 112 patients whom end of study data was available on FAS.

Arm/Group Title	NPC-01
Arm/Group Description	Norethisterone, Ethinyl Estradiol NPC-01: This study consist of the following steps. Step 1(Norethisterone 0.6mg, Ethinyl Estradiol 0.035mg):From first study medication to 3th menstrual cycles. Step 2(Norethisterone 1mg, Ethinyl Estradiol 0.035mg): After interim analysis of the results of step 1, in the case of the efficacy results meet prespecified criterion, same dose level will be continued to 13th menstrual cycles including step 1. If the results do not meet prespecified criterion, the dose will be increased to Norethisterone 1mg, Ethinyl Estradiol 0.035mg and be continued newly until 13th menstrual cycle from this point.
Measure Participants	112
Mean (Standard Deviation) [units on a scale]	2.4 (1.80)

2. Secondary Outcome

Title	Difference in the Visual Analog Scale (VAS) of Dysmenorrhea (Baseline/Pretreatment-dnd of Treatment)
Description	VAS stands for Visual Analogue Scale of pain. The scale was rated as a graphic rating scale. as a 100mm baseline from 0:No pain to 100:Worst possible pain.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

This analysis was carried out for 112 patients whom end of study data was available on FAS.

Arm/Group Title	NPC-01
Arm/Group Description	Norethisterone, Ethinyl Estradiol NPC-01: This study consist of the following steps. Step 1(Norethisterone 0.6mg, Ethinyl Estradiol 0.035mg):From first study medication to 3th menstrual cycles. Step 2(Norethisterone 1mg, Ethinyl Estradiol 0.035mg): After interim analysis of the results of step 1, in the case of the efficacy results meet prespecified criterion, same dose level will be continued to 13th menstrual cycles including step 1. If the results do not meet prespecified criterion, the dose will be increased to Norethisterone 1mg, Ethinyl Estradiol 0.035mg and be continued newly until 13th menstrual cycle from this point.
Measure Participants	112
Mean (Standard Deviation) [units on a scale]	28.4 (25.13)

Adverse Events

Time Frame	From study administration to 15 cycles of menstruation, an average of 14 months
Arm/Group Title	NPC-01
Arm/Group Description	Norethisterone, Ethinyl Estradiol NPC-01: This study consist of the following steps. Step 1(Norethisterone 0.6mg, Ethinyl Estradiol 0.035mg):From first study medication to 3th menstrual cycles. Step 2(Norethisterone 1mg, Ethinyl Estradiol 0.035mg): After interim analysis of the results of step 1, in the case of the efficacy results meet prespecified criterion, same dose level will be continued to 13th menstrual cycles including step 1. If the results do not meet prespecified criterion, the dose will be increased to Norethisterone 1mg, Ethinyl Estradiol 0.035mg and be continued newly until 13th menstrual cycle from this point.
All Cause Mortality
	NPC-01
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	NPC-01
	Affected / at Risk (%)	# Events
Total	5/147 (3.4%)
Infections and infestations
Cellulitis orbital	1/147 (0.7%)	1
Nervous system disorders
Depressed level of consciousness	1/147 (0.7%)	1
Reproductive system and breast disorders
Endometriosis	1/147 (0.7%)	1
Vascular disorders
Haemorrhagic ovrian cyst	2/147 (1.4%)	2
Other (Not Including Serious) Adverse Events
	NPC-01
	Affected / at Risk (%)	# Events
Total	147/147 (100%)
Gastrointestinal disorders
Abdominal discomfort	11/147 (7.5%)	20
Abdominal pain upper	17/147 (11.6%)	29
Constipation	10/147 (6.8%)	10
Dental caries	12/147 (8.2%)	13
Diarrhoea	14/147 (9.5%)	34
Gastritis	9/147 (6.1%)	9
Nausea	25/147 (17%)	42
General disorders
Malaise	13/147 (8.8%)	17
Infections and infestations
Cystitis	9/147 (6.1%)	9
Gastroenteritis	13/147 (8.8%)	14
Influenza	12/147 (8.2%)	12
Nasopharyngitis	95/147 (64.6%)	242
Investigations
Blood triglycerides increased	9/147 (6.1%)	11
Weight increased	10/147 (6.8%)	10
Protein urine present	8/147 (5.4%)	8
Musculoskeletal and connective tissue disorders
Back pain	11/147 (7.5%)	13
Nervous system disorders
Headache	53/147 (36.1%)	220
Reproductive system and breast disorders
Amenorrhoea	10/147 (6.8%)	11
Hypomenorrhoea	22/147 (15%)	27
Menorrhagia	24/147 (16.3%)	42
Metrorrhagia	132/147 (89.8%)	916
Oligomenorrhoea	67/147 (45.6%)	135
Polymenorrhoea	19/147 (12.9%)	29
Breast discomfort	8/147 (5.4%)	11
Haemorrhagic ovarian cyst	14/147 (9.5%)	14
Skin and subcutaneous tissue disorders
Acnes	8/147 (5.4%)	9

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is an agreement between the sponsor and PI that no restricts the PI's right but need to discuss the timing of publish date of trial results after the trial is completed.