Trial Outcomes & Findings for A Combination Trial of Copaxone Plus Estriol in Relapsing Remitting Multiple Sclerosis (RRMS) (NCT NCT00451204)

Last Updated: 2016-06-16

Results Overview

A confirmed relapse was defined as new neurological symptoms or worsening of pre-existing symptoms, lasting at least 48 hours in a subject who had been neurologically stable or improving in the previous 30 days, accompanied by objective change in the neurological examination (worsening of 0.5 points on the EDSS or worsening by 1.0 or more points on the pyramidal, cerebellar, brainstem or visual functional system scores), not due to fatigue alone and not associated with fever or infection.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

158 participants

Primary outcome timeframe

24 months

Results posted on

2016-06-16

Participant Flow

Participant milestones

Participant milestones
Measure	Estriol Capsules Plus Copaxone Injections Estriol: Estriol 8 mg capsule, once per day, duration of treatment is 2 years	Placebo Capsules Plus Copaxone Injections Placebo: Placebo capsule, once per day, treatment duration is 2 years
Overall Study STARTED	82	76
Overall Study COMPLETED	60	56
Overall Study NOT COMPLETED	22	20

Reasons for withdrawal

Reasons for withdrawal
Measure	Estriol Capsules Plus Copaxone Injections Estriol: Estriol 8 mg capsule, once per day, duration of treatment is 2 years	Placebo Capsules Plus Copaxone Injections Placebo: Placebo capsule, once per day, treatment duration is 2 years
Overall Study Adverse Event	4	6
Overall Study Lack of Efficacy	4	4
Overall Study Lost to Follow-up	4	4
Overall Study Protocol Violation	1	0
Overall Study Patient refusal	8	4
Overall Study Other	1	2

Baseline Characteristics

A Combination Trial of Copaxone Plus Estriol in Relapsing Remitting Multiple Sclerosis (RRMS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Estriol Capsules Plus Copaxone Injections n=82 Participants Estriol: Estriol 8 mg capsule, once per day, duration of treatment is 2 years	Placebo Capsules Plus Copaxone Injections n=76 Participants Placebo: Placebo capsule, once a day, treatment duration is 2 years	Total n=158 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
Age, Categorical Between 18 and 65 years	82 Participants n=5 Participants	76 Participants n=7 Participants	158 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	37.7 years STANDARD_DEVIATION 7.6 • n=5 Participants	37.1 years STANDARD_DEVIATION 7.3 • n=7 Participants	37.4 years STANDARD_DEVIATION 7.45 • n=5 Participants
Sex: Female, Male Female	82 Participants n=5 Participants	76 Participants n=7 Participants	158 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	82 participants n=5 Participants	76 participants n=7 Participants	158 participants n=5 Participants

PRIMARY outcome

Timeframe: 24 months

Population: Included all as intention to treat

Outcome measures

Outcome measures
Measure	Estriol Capsules Plus Copaxone Injections n=82 Participants Estriol: Estriol 8 mg capsule, once per day, duration of treatment is 2 years	Placebo Capsules Plus Copaxone Injections n=76 Participants Placebo: Placebo capsule, once a day, treatment duration is 2 years
Confirmed Relapse, Annualized Relapse Rate	0.25 relapses per year Interval 0.17 to 0.37	0.37 relapses per year Interval 0.25 to 0.53

SECONDARY outcome

Timeframe: 24 months

Population: Included all as intention to treat.

Met all criteria for relapse except not confirmed to have increase in EDSS by an independent examiner.

Outcome measures

Outcome measures
Measure	Estriol Capsules Plus Copaxone Injections n=82 Participants Estriol: Estriol 8 mg capsule, once per day, duration of treatment is 2 years	Placebo Capsules Plus Copaxone Injections n=76 Participants Placebo: Placebo capsule, once a day, treatment duration is 2 years
Relapse Event, Annualized Relapse Rate	0.32 relapses per year Interval 0.22 to 0.46	0.46 relapses per year Interval 0.32 to 0.65

SECONDARY outcome

Timeframe: 24 months

Population: All included as intention to treat

Outcome measures

Outcome measures
Measure	Estriol Capsules Plus Copaxone Injections n=82 Participants Estriol: Estriol 8 mg capsule, once per day, duration of treatment is 2 years	Placebo Capsules Plus Copaxone Injections n=76 Participants Placebo: Placebo capsule, once a day, treatment duration is 2 years
Confirmed Relapse, Probability of First Relapse	33.3 probability of relapse at 24 months Interval 23.8 to 45.4	42.9 probability of relapse at 24 months Interval 32.1 to 55.5

SECONDARY outcome

Timeframe: 24 months

Population: Included all as intention to treat

Outcome measures

Outcome measures
Measure	Estriol Capsules Plus Copaxone Injections n=82 Participants Estriol: Estriol 8 mg capsule, once per day, duration of treatment is 2 years	Placebo Capsules Plus Copaxone Injections n=76 Participants Placebo: Placebo capsule, once a day, treatment duration is 2 years
Relapse Event, Probability of First Relapse Event	40.5 probability of relapse event at 24 mo Interval 30.0 to 53.0	46.9 probability of relapse event at 24 mo Interval 35.9 to 59.3

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 months

Outcome measures

Outcome measures
Measure	Estriol Capsules Plus Copaxone Injections n=82 Participants Estriol: Estriol 8 mg capsule, once per day, duration of treatment is 2 years	Placebo Capsules Plus Copaxone Injections n=76 Participants Placebo: Placebo capsule, once a day, treatment duration is 2 years
Confirmed Relapse, Annualized Relapse Rate	0.25 relapses per year Interval 0.16 to 0.4	0.48 relapses per year Interval 0.33 to 0.69

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 months

Met all criteria for relapse except not confirmed to have increase in EDSS by an independent examiner.

Outcome measures

Outcome measures
Measure	Estriol Capsules Plus Copaxone Injections n=82 Participants Estriol: Estriol 8 mg capsule, once per day, duration of treatment is 2 years	Placebo Capsules Plus Copaxone Injections n=76 Participants Placebo: Placebo capsule, once a day, treatment duration is 2 years
Relapse Event, Annualized Relapse Rate	0.33 relapses per year Interval 0.22 to 0.5	0.61 relapses per year Interval 0.44 to 0.84

Adverse Events

Estriol Capsules Plus Copaxone Injections

Serious events: 8 serious events

Other events: 76 other events

Deaths: 0 deaths

Placebo Capsules Plus Copaxone Injections

Serious events: 10 serious events

Other events: 67 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Estriol Capsules Plus Copaxone Injections n=82 participants at risk Estriol: Estriol 8 mg capsule, once per day, duration of treatment is 2 years	Placebo Capsules Plus Copaxone Injections n=76 participants at risk Placebo: Placebo capsule, once a day, treatment duration is 2 years
Nervous system disorders MS Relapse (hospitalization)	2.4% 2/82 • Number of events 2 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.	6.6% 5/76 • Number of events 6 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.
Pregnancy, puerperium and perinatal conditions Pregnancy	2.4% 2/82 • Number of events 2 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.	0.00% 0/76 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.
Infections and infestations Urinary Tract Infection	1.2% 1/82 • Number of events 1 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.	1.3% 1/76 • Number of events 1 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.
Eye disorders Migraine headache related eye pain	1.2% 1/82 • Number of events 1 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.	0.00% 0/76 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.
Cardiac disorders Heart Failure/ pace maker implantation	1.2% 1/82 • Number of events 1 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.	0.00% 0/76 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.
Renal and urinary disorders Pyelonephritis	1.2% 1/82 • Number of events 1 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.	0.00% 0/76 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.
Investigations Accidentally took other's drug	0.00% 0/82 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.	1.3% 1/76 • Number of events 1 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.
Infections and infestations Acute appendicitis	0.00% 0/82 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.	1.3% 1/76 • Number of events 1 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) B-cell lymphoma	0.00% 0/82 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.	1.3% 1/76 • Number of events 1 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.
Injury, poisoning and procedural complications car accident related body numbness	0.00% 0/82 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.	1.3% 1/76 • Number of events 1 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.
Musculoskeletal and connective tissue disorders Right Knee Replacemebt	0.00% 0/82 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.	1.3% 1/76 • Number of events 1 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.

Other adverse events

Additional Information

Dr. Rhonda Voskuhl

University of California Los Angeles

Phone: 310-206-4636

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Estriol Capsules Plus Copaxone Injections n=82 participants at risk Estriol: Estriol 8 mg capsule, once per day, duration of treatment is 2 years	Placebo Capsules Plus Copaxone Injections n=76 participants at risk Placebo: Placebo capsule, once a day, treatment duration is 2 years
Infections and infestations Upper respiratory Infection	26.8% 22/82 • Number of events 33 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.	34.2% 26/76 • Number of events 38 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.
Skin and subcutaneous tissue disorders GA injection area abnormalities	25.6% 21/82 • Number of events 25 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.	15.8% 12/76 • Number of events 15 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.
Reproductive system and breast disorders Irregular menses/ spotting	23.2% 19/82 • Number of events 26 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.	3.9% 3/76 • Number of events 4 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.
Renal and urinary disorders Urinary tract infection	18.3% 15/82 • Number of events 23 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.	13.2% 10/76 • Number of events 16 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.
General disorders Fatigue	15.9% 13/82 • Number of events 15 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.	10.5% 8/76 • Number of events 10 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.
Psychiatric disorders Depression/ Anxiety	14.6% 12/82 • Number of events 14 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.	11.8% 9/76 • Number of events 10 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.
Reproductive system and breast disorders Menstrual flow amount increased	13.4% 11/82 • Number of events 12 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.	7.9% 6/76 • Number of events 8 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.
General disorders Headache	11.0% 9/82 • Number of events 11 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.	14.5% 11/76 • Number of events 12 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.
Gastrointestinal disorders Nausea/ vomitting	8.5% 7/82 • Number of events 9 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.	6.6% 5/76 • Number of events 5 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.
General disorders GA injection systemic reaction (SOB, hot flashes)	8.5% 7/82 • Number of events 7 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.	2.6% 2/76 • Number of events 2 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.
Respiratory, thoracic and mediastinal disorders Sinusitis	7.3% 6/82 • Number of events 6 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.	13.2% 10/76 • Number of events 14 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.
Nervous system disorders Arm/ leg numbness, tingling	7.3% 6/82 • Number of events 7 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.	9.2% 7/76 • Number of events 10 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.
Gastrointestinal disorders Gastroenteritis	6.1% 5/82 • Number of events 7 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.	3.9% 3/76 • Number of events 4 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.
Nervous system disorders Dizziness	4.9% 4/82 • Number of events 5 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.	9.2% 7/76 • Number of events 10 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.
Eye disorders Vision problem (blurry, double)	4.9% 4/82 • Number of events 6 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.	9.2% 7/76 • Number of events 7 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.
General disorders Back Pain	4.9% 4/82 • Number of events 5 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.	6.6% 5/76 • Number of events 5 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.
Reproductive system and breast disorders Menstrual cramp	4.9% 4/82 • Number of events 4 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.	5.3% 4/76 • Number of events 5 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.
General disorders Insomnia	4.9% 4/82 • Number of events 4 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.	5.3% 4/76 • Number of events 4 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.
Cardiac disorders Heart palpitation	2.4% 2/82 • Number of events 2 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.	5.3% 4/76 • Number of events 4 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.
Skin and subcutaneous tissue disorders Shingles	2.4% 2/82 • Number of events 2 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.	5.3% 4/76 • Number of events 4 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.
Reproductive system and breast disorders Vaginal infection	1.2% 1/82 • Number of events 1 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.	10.5% 8/76 • Number of events 9 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.
Reproductive system and breast disorders Uterus, endometrial thickness > 8mm (ultrasound)	29.3% 24/82 • Number of events 29 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.	35.5% 27/76 • Number of events 36 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.
Reproductive system and breast disorders Uterus, endometrial biopsies performed	11.0% 9/82 • Number of events 11 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.	7.9% 6/76 • Number of events 8 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.
Reproductive system and breast disorders Uterus, fibroibds (ultrasound)	9.8% 8/82 • Number of events 10 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.	10.5% 8/76 • Number of events 11 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.
Reproductive system and breast disorders Fibrocystic disease on clinical exam	6.1% 5/82 • Number of events 6 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.	5.3% 4/76 • Number of events 5 • After enrollment, during the 24-month treatment period An adverse event is any condition that occurs after enrollment, whether or not considered related to study treatment.