Elagolix Versus Subcutaneous Depot Medroxyprogesterone Acetate for the Treatment of Endometriosis

Endometriosis Clinical Trial

— PETAL  

Official title:

A Phase II, Randomized, Double-blind, Active-controlled Study to Assess the Safety and Efficacy of NBI-56418 in Subjects With Endometriosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00437658
• Other study ID #: NBI-56418-0603
• Status: Completed
• Phase: Phase 2
• Start date: December 11, 2006
• Est. completion date: November 24, 2008

Study information

• Verified date: March 2018
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is designed to assess the effects of elagolix versus subcutaneous depot medroxyprogesterone acetate (DMPA-SC; also known as depo-provera) on bone mineral density (BMD) during treatment for 24 weeks with a subsequent 24-week post-treatment period.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 252
• Est. completion date: November 24, 2008
• Est. primary completion date: November 24, 2008
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 49 Years

Eligibility

Inclusion Criteria:

• Be female, aged 18 to 49 years, inclusive

• Have a total CPSSS of = 6 at screening and baseline (Day 1) in the following categories: dysmenorrhea, dyspareunia, nonmenstrual pelvic pain, pelvic tenderness and induration. The total score must include a total of at least 2 in each of the categories of dysmenorrhea and nonmenstrual pelvic pain.

• Have had a diagnosis of endometriosis made following laparoscopic visualization of the disease within 8 years of the start of screening with recurrent or persistent symptoms.

• Have documented negative mammogram results within 12 months of screening if over the age of 40 years.

• Have menstrual cycles (28 days ±5 days). Assessment of cycle duration should be based on observations in the absence of drugs or conditions that are known to affect the cycle (e.g., oral contraceptives, leuprolide, pregnancy).

• Have a Body Mass Index (BMI) between 18 and 36 kg/m², inclusive.

• Agree to use two forms of nonhormonal contraception (e.g. condom with spermicide) during the study.

Exclusion Criteria:

• Are currently receiving gonadotropin-releasing hormone (GnRH) agonist, GnRH antagonist, danazol, or have received any of these agents within 6 months of the start of screening.

• Are currently receiving subcutaneous medroxyprogesterone acetate (DMPA-SC) or intramuscular medroxyprogesterone acetate (DMPA-IM) or have received any of these agents within 3 months of the start of screening.

• Have been nonresponsive to GnRH agonist or antagonist therapy for the management of endometriosis.

• Are currently using hormonal contraception or other forms of hormonal therapy or received such treatment within 1 month of the start of screening.

• Have had surgical treatment for endometriosis (laparoscopy) within 1 month of the start of screening.

• Have had a hysterectomy or bilateral oophorectomy.

• Have had prior treatment with NBI-56418.

• Have uterine fibroids or other pelvic lesions = 5 cm in diameter

• Have any of the following abnormal cervical smear results at screening (based on the 2001 Bethesda System):

• Benign endometrial cells (BEC) present, provided subject has irregular uterine bleeding or is over 40 years old

• Atypical squamous cells of undetermined significance (ASC-US) present, and human papilloma virus (HPV) reflex testing is positive for high risk types or the testing outcome is unknown

• Atypical squamous cells present, and high-grade squamous intraepithelial lesion (ASC-H) cannot be excluded

• Atypical glandular cells of uncertain significance (AGUS/AGC): not otherwise specified (NOS), favor neoplasia (FN), favor endocervical, or favor endometrial origin types

• Low-grade squamous intraepithelial lesion (LSIL) present

• High-grade squamous intraepithelial lesion (HSIL) present

• Adenocarcinoma in situ (AIS) / malignant cells present

• Have BMD with either lumbar spine or femur T-scores below -1.5 at screening as determined by the central DXA facility or have history of pathologic or compression fractures.

• Have been pregnant within 6 months of screening or currently breast feeding

• Are using systemic steroids on a chronic or regular basis within 3 months

• Have unstable medical condition or chronic disease

• Have chronic pelvic pain that is not caused by endometriosis

Related Conditions & MeSH terms

• Endometriosis

Intervention

Drug:
• Elagolix
Provided as tablets for oral administration
• Subcutaneous depot medroxyprogesterone acetate (DMPA-SC)
Provided for subcutaneous injection in a prefilled syringe, 104 mg/0.65 mL per syringe.
• Placebo to Elagolix
Matching placebo tablets for oral administration
• Placebo to DMPA-SC
Matching placebo for subcutaneous injection in a pre-filled syringe

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change From Baseline in Bone Mineral Density of the Spine at Week 24	Bone mineral density (BMD) was measured by dual X-ray absorptiometry (DXA). The percent change from baseline in spine and femur BMD at week 24 was assessed using a one-way analysis of variance (ANOVA) model. The absence of significant bone loss was supported if the lower bounds of the confidence intervals for the mean percent change in BMD were = -2.2% for both the spine and femur at week 24.	Baseline and week 24
Primary	Percent Change From Baseline in Bone Mineral Density of the Femur at Week 24	Bone mineral density (BMD) was measured by dual X-ray absorptiometry (DXA). The percent change from baseline in spine and femur BMD at week 24 was assessed using a one-way analysis of variance (ANOVA) model. The absence of significant bone loss was supported if the lower bounds of the confidence intervals for the mean percent change in BMD were = -2.2% for both the spine and femur at week 24.	Baseline and week 24
Secondary	Percent Change From Baseline in Bone Mineral Density of the Spine at Weeks 12 and 48	Bone mineral density (BMD) was measured by dual X-ray absorptiometry (DXA). The percent change from baseline in BMD was assessed using a one-way analysis of variance (ANOVA) model.	Baseline and weeks 12 and 48
Secondary	Percent Change From Baseline in Bone Mineral Density of the Femur at Weeks 12 and 48	Bone mineral density (BMD) was measured by dual X-ray absorptiometry (DXA). The percent change from baseline in BMD was assessed using a one-way analysis of variance (ANOVA) model.	Baseline and weeks 12 and 48
Secondary	Change From Baseline in N-telopeptide at Weeks 12, 24 and 48	Blood samples to determine N-telopeptide concentrations were analyzed by a central laboratory using an enzyme-linked immunosorbent assay (ELISA). Change from baseline in N-telopeptide was analyzed using a one-way ANOVA model.	Baseline and weeks 12, 24 and 48
Secondary	Percentage of Participants With a Response in the Dysmenorrhea Component of the Composite Pelvic Signs and Symptoms Score (CPSSS) at Week 24	The CPSSS consists of 5 components that address dysmenorrhea (pain during menstruation), dyspareunia (painful intercourse), non-menstrual pelvic pain, pelvic tenderness, and pelvic induration (hardening). Each component was scored on a scale of 0 to 3 (0 = absent, 1 = mild, 2 = moderate, and 3 = severe). The dysmenorrhea score was based on the participant's response to the question "Have you had painful menstruation during the last 28 days?".; Participants were classified as responders for dysmenorrhea if they reported a 1 point or greater reduction (improvement) from baseline.	Baseline and week 24
Secondary	Percentage of Participants With a Response in the Non-menstrual Pelvic Pain Component of the CPSSS at Week 24	The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration. Each component was scored on a scale of 0 to 3 (0 = absent, 1 = mild, 2 = moderate, and 3 = severe). The non-menstrual pelvic pain score was based on participant's response to the question "Have you had pelvic pain during the last 28 days?" Participants were classified as responders for non-menstrual pelvic pain if they reported a 1 point or greater reduction (improvement) from baseline.	Baseline and week 24
Secondary	Percentage of Participants With a Response in the Dysmenorrhea Component of the CPSSS Over Time	The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration. Each component was scored on a scale of 0 to 3 (0 = absent, 1 = mild, 2 = moderate, and 3 = severe). The dysmenorrhea score was based on the participant's response to the question "Have you had painful menstruation during the last 28 days?".; Participants were classified as responders for dysmenorrhea if they reported a 1 point or greater reduction (improvement) from baseline.	Baseline and weeks 4, 8, 12, 16, 20, 24, 28, 36, and 48
Secondary	Percentage of Participants With a Response in the Non-menstrual Pelvic Pain Component of the CPSSS Over Time	The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration. Each component was scored on a scale of 0 to 3 (0 = absent, 1 = mild, 2 = moderate, and 3 = severe). The non-menstrual pelvic pain score was based on participant's response to the question "Have you had pelvic pain during the last 28 days?" Participants were classified as responders for non-menstrual pelvic pain if they reported a 1 point or greater reduction (improvement) from baseline.	Baseline and weeks 4, 8, 12, 16, 20, 24, 28, 36, and 48
Secondary	Change From Baseline in Total CPSSS During the Treatment Period	The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration. Each component was scored on a scale of 0 to 3 (0 = absent, 1 = mild, 2 = moderate, and 3 = severe).; Dysmenorrhea, dyspareunia, and nonmenstrual pelvic pain scores are based on the participant's assessment, pelvic tenderness and induration were assessed by the investigator based on findings associated with a pelvic examination.; The total CPSSS has a maximum possible value of 15 (total score range: 0 to 15, where a lower score indicates less signs and symptoms of endometriosis or better functioning).; Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.	Baseline and weeks 4, 8, 12, 16, 20, and 24
Secondary	Change From Baseline in Total CPSSS Excluding Dyspareunia During the Treatment Period	The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration. Each component was scored on a scale of 0 to 3 (0 = absent, 1 = mild, 2 = moderate, and 3 = severe).; Dysmenorrhea, dyspareunia, and nonmenstrual pelvic pain scores are based on the participant's assessment, pelvic tenderness and induration were assessed by the investigator based on findings associated with a pelvic examination.; The total CPSSS excluding dyspareunia has a maximum possible value of 12 (total score range: 0 to 12, where a lower score indicates less signs and symptoms of endometriosis or better functioning).; Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.	Baseline and weeks 4, 8, 12, 16, 20, and 24
Secondary	Change From Baseline in Dysmenorrhea Component of the CPSSS During the Treatment Period	The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration. Each component was scored on a scale of 0 to 3 (0 = absent, 1 = mild, 2 = moderate, and 3 = severe).; The dysmenorrhea score was based on the participant's response to the question "Have you had painful menstruation during the last 28 days?".; Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.	Baseline and weeks 4, 8, 12, 16, 20, and 24
Secondary	Change From Baseline in Dyspareunia Component of the CPSSS During the Treatment Period	The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration. Each component was scored on a scale of 0 to 3 (0 = absent, 1 = mild, 2 = moderate, and 3 = severe).; The dyspareunia score was based on the participant's response to the question "Have you had painful intercourse during the last 28 days?" Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.	Baseline and weeks 4, 8, 12, 16, 20, and 24
Secondary	Change From Baseline in Non-menstrual Pelvic Pain Component of the CPSSS During the Treatment Period	The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration. Each component was scored on a scale of 0 to 3 (0 = absent, 1 = mild, 2 = moderate, and 3 = severe).; The non-menstrual pelvic pain score was based on participant's response to the question "Have you had pelvic pain during the last 28 days?".; Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.	Baseline and weeks 4, 8, 12, 16, 20, and 24
Secondary	Change From Baseline in Pelvic Tenderness Component of the CPSSS During the Treatment Period	The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration. Each component was scored on a scale of 0 to 3 (0 = absent, 1 = mild, 2 = moderate, and 3 = severe).; Pelvic tenderness was assessed by the investigator based on findings associated with a pelvic examination.; Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.	Baseline and weeks 4, 8, 12, 16, 20, and 24
Secondary	Change From Baseline in Pelvic Induration Component of the CPSSS During the Treatment Period	The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration. Each component was scored on a scale of 0 to 3 (0 = absent, 1 = mild, 2 = moderate, and 3 = severe).; Pelvic induration was assessed by the investigator based on findings associated with a pelvic examination.; Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.	Baseline and weeks 4, 8, 12, 16, 20, and 24
Secondary	Change From Baseline in in Monthly Peak Visual Analog Scale (VAS) for Pelvic Pain	The VAS for pelvic pain was used as an assessment of pain intensity. The VAS was a horizontal line on which the left extreme was labeled "no pain" and the right extreme was labeled "worst pain ever felt" scored on a scale from of 0 (no pain) to 100 (worst pain ever felt). Participants indicated the worst level of pain felt over a 24-hour period by ''ticking'' the horizontal line on their e-Diary at approximately the same time each day. Monthly peak VAS for pelvic pain was defined as the maximum VAS pain score reported for an individual participant from the previous visit to the day of the current scheduled visit.; Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.	Baseline and weeks 4, 8, 12, 16, 20, and 24
Secondary	Change From Baseline in in Monthly Mean Visual Analog Scale (VAS) for Pelvic Pain	The VAS for pelvic pain was used as an assessment of pain intensity. The VAS was a horizontal line on which the left extreme was labeled "no pain" and the right extreme was labeled "worst pain ever felt" scored on a scale from of 0 (no pain) to 100 (worst pain ever felt). Participants indicated the worst level of pain felt over a 24-hour period by ''ticking'' the horizontal line on their e-Diary at approximately the same time each day. Monthly mean VAS for pelvic pain defined as the average of all VAS pain scores reported for an individual participant from the previous visit to the day of the current scheduled visit.; Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.	Baseline and weeks 4, 8, 12, 16, 20, and 24
Secondary	Change From Baseline in Endometriosis Health Profile-5 (EHP-5) Pain Dimension	The EHP-5 is an instrument to measure health-related quality of life in women with endometriosis. The EHP-5 consists of two parts: A core questionnaire consisting of five questions that measure the areas of pain, control and powerlessness, emotional well-being, social support, and self-image; A supplemental questionnaire consisting of six additional questions, five of which were recorded in this study: work, relationship with children, sexual intercourse, feelings about the medical profession and treatment.; Each question was scored on a five point scale (Never = 0, Rarely = 25, Sometimes = 50, Often = 75, Always = 100), where 0 indicates the best health status and 100 worst health status. A negative change from baseline score indicates improvement in quality of life.	Baseline and weeks 4, 8, 12, 16, 20, and 24
Secondary	Change From Baseline in EHP-5 Control and Powerlessness Dimension	The EHP-5 is an instrument to measure health-related quality of life in women with endometriosis. The EHP-5 consists of two parts: A core questionnaire consisting of five questions that measure the areas of pain, control and powerlessness, emotional well-being, social support, and self-image; A supplemental questionnaire consisting of six additional questions, five of which were recorded in this study: work, relationship with children, sexual intercourse, feelings about the medical profession and treatment.; Each question was scored on a five point scale (Never = 0, Rarely = 25, Sometimes = 50, Often = 75, Always = 100), where 0 indicates the best health status and 100 worst health status. A negative change from baseline score indicates improvement in quality of life.	Baseline and weeks 4, 8, 12, 16, 20, and 24
Secondary	Change From Baseline in EHP-5 Emotional Well-being Dimension	The EHP-5 is an instrument to measure health-related quality of life in women with endometriosis. The EHP-5 consists of two parts: A core questionnaire consisting of five questions that measure the areas of pain, control and powerlessness, emotional well-being, social support, and self-image; A supplemental questionnaire consisting of six additional questions, five of which were recorded in this study: work, relationship with children, sexual intercourse, feelings about the medical profession and treatment.; Each question was scored on a five point scale (Never = 0, Rarely = 25, Sometimes = 50, Often = 75, Always = 100), where 0 indicates the best health status and 100 worst health status. A negative change from baseline score indicates improvement in quality of life.	Baseline and weeks 4, 8, 12, 16, 20, and 24
Secondary	Change From Baseline in EHP-5 Social Support Dimension	The EHP-5 is an instrument to measure health-related quality of life in women with endometriosis. The EHP-5 consists of two parts: A core questionnaire consisting of five questions that measure the areas of pain, control and powerlessness, emotional well-being, social support, and self-image; A supplemental questionnaire consisting of six additional questions, five of which were recorded in this study: work, relationship with children, sexual intercourse, feelings about the medical profession and treatment.; Each question was scored on a five point scale (Never = 0, Rarely = 25, Sometimes = 50, Often = 75, Always = 100), where 0 indicates the best health status and 100 worst health status. A negative change from baseline score indicates improvement in quality of life.	Baseline and weeks 4, 8, 12, 16, 20, and 24
Secondary	Change From Baseline in EHP-5 Self Image Dimension	The EHP-5 is an instrument to measure health-related quality of life in women with endometriosis. The EHP-5 consists of two parts: A core questionnaire consisting of five questions that measure the areas of pain, control and powerlessness, emotional well-being, social support, and self-image; A supplemental questionnaire consisting of six additional questions, five of which were recorded in this study: work, relationship with children, sexual intercourse, feelings about the medical profession and treatment.; Each question was scored on a five point scale (Never = 0, Rarely = 25, Sometimes = 50, Often = 75, Always = 100), where 0 indicates the best health status and 100 worst health status. A negative change from baseline score indicates improvement in quality of life.	Baseline and weeks 4, 8, 12, 16, 20, and 24
Secondary	Change From Baseline in EHP-5 Work Dimension	The EHP-5 is an instrument to measure health-related quality of life in women with endometriosis. The EHP-5 consists of two parts: A core questionnaire consisting of five questions that measure the areas of pain, control and powerlessness, emotional well-being, social support, and self-image; A supplemental questionnaire consisting of six additional questions, five of which were recorded in this study: work, relationship with children, sexual intercourse, feelings about the medical profession and treatment.; Each question was scored on a five point scale (Never = 0, Rarely = 25, Sometimes = 50, Often = 75, Always = 100), or Not Relevant (no score), where 0 indicates the best health status and 100 worst health status. A negative change from baseline score indicates improvement in quality of life.	Baseline and weeks 4, 8, 12, 16, 20, and 24
Secondary	Change From Baseline in EHP-5 Relationship With Children Dimension	The EHP-5 is an instrument to measure health-related quality of life in women with endometriosis. The EHP-5 consists of two parts: A core questionnaire consisting of five questions that measure the areas of pain, control and powerlessness, emotional well-being, social support, and self-image; A supplemental questionnaire consisting of six additional questions, five of which were recorded in this study: work, relationship with children, sexual intercourse, feelings about the medical profession and treatment.; Each question was scored on a five point scale (Never = 0, Rarely = 25, Sometimes = 50, Often = 75, Always = 100), or Not Relevant (no score), where 0 indicates the best health status and 100 worst health status. A negative change from baseline score indicates improvement in quality of life.	Baseline and weeks 4, 8, 12, 16, 20, and 24
Secondary	Change From Baseline in EHP-5 Intercourse Dimension	The EHP-5 is an instrument to measure health-related quality of life in women with endometriosis. The EHP-5 consists of two parts: A core questionnaire consisting of five questions that measure the areas of pain, control and powerlessness, emotional well-being, social support, and self-image; A supplemental questionnaire consisting of six additional questions, five of which were recorded in this study: work, relationship with children, sexual intercourse, feelings about the medical profession and treatment.; Each question was scored on a five point scale (Never = 0, Rarely = 25, Sometimes = 50, Often = 75, Always = 100), or Not Relevant (no score), where 0 indicates the best health status and 100 worst health status. A negative change from baseline score indicates improvement in quality of life.	Baseline and weeks 4, 8, 12, 16, 20, and 24
Secondary	Change From Baseline in EHP-5 Medical Profession Dimension	The EHP-5 is an instrument to measure health-related quality of life in women with endometriosis. The EHP-5 consists of two parts: A core questionnaire consisting of five questions that measure the areas of pain, control and powerlessness, emotional well-being, social support, and self-image; A supplemental questionnaire consisting of six additional questions, five of which were recorded in this study: work, relationship with children, sexual intercourse, feelings about the medical profession and treatment.; Each question was scored on a five point scale (Never = 0, Rarely = 25, Sometimes = 50, Often = 75, Always = 100), or Not Relevant (no score), where 0 indicates the best health status and 100 worst health status. A negative change from baseline score indicates improvement in quality of life.	Baseline and weeks 4, 8, 12, 16, 20, and 24
Secondary	Change From Baseline in EHP-5 Treatment Dimension	The EHP-5 is an instrument to measure health-related quality of life in women with endometriosis. The EHP-5 consists of two parts: A core questionnaire consisting of five questions that measure the areas of pain, control and powerlessness, emotional well-being, social support, and self-image; A supplemental questionnaire consisting of six additional questions, five of which were recorded in this study: work, relationship with children, sexual intercourse, feelings about the medical profession and treatment.; Each question was scored on a five point scale (Never = 0, Rarely = 25, Sometimes = 50, Often = 75, Always = 100), or Not Relevant (no score), where 0 indicates the best health status and 100 worst health status. A negative change from baseline score indicates improvement in quality of life.	Baseline and weeks 4, 8, 12, 16, 20, and 24
Secondary	Percentage of Participants Using Analgesics During the Treatment Phase	Analgesic use was collected as part of concomitant medications on a case report form that was administered at each scheduled visit.	24 weeks