SPIRIT 1: Efficacy and Safety Study of Relugolix in Women With Endometriosis-Associated Pain

Sponsor

Myovant Sciences GmbH (Industry)

Overall Status

Completed

CT.gov ID

NCT03204318

Collaborator

(none)

638

Enrollment

123

Locations

Arms

Actual Duration (Months)

5.2

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the benefit and safety of relugolix 40 milligrams (mg) once daily, co-administered with low-dose estradiol (E2) and norethindrone acetate (NETA) compared with placebo for 24 weeks, on dysmenorrhea and on nonmenstrual pelvic pain.

Condition or Disease	Intervention/Treatment	Phase
Endometriosis Related Pain	Drug: Relugolix Drug: Estradiol/norethindrone acetate Drug: Estradiol/norethindrone acetate placebo Drug: Relugolix placebo	Phase 3

Detailed Description

This study is an international phase 3 randomized, double-blind, placebo-controlled efficacy and safety study to evaluate 24 weeks of oral, once-daily relugolix (40 mg) co-administered with either 12 or 24 weeks of low-dose E2 (1.0 mg) and NETA (0.5 mg), compared with placebo.

Approximately 600 women with endometriosis-associated pain will be enrolled and randomized 1:1:1 to Group A - relugolix plus low-dose hormonal add-back therapy, Group B - relugolix monotherapy for 12 weeks followed by co-administration with low-dose hormonal add-back therapy, or Group C - placebo (N = 200 per group).

Eligible participants were randomized on Baseline Day 1 to Treatment Group A, B, or C, in the double-blind period.

Eligible participants, including those randomized to placebo, were offered the opportunity to enroll in an 80-week open-label extension study where participants received relugolix co-administered with low-dose E2 and NETA. Participants who did not enroll into the extension study had a Follow-Up visit approximately 30 days after the participant's last dose of study drug.

Study Design

Study Type:

Interventional

Actual Enrollment :

638 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

SPIRIT 1: An International Phase 3 Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study to Evaluate Relugolix Administered With and Without Low-Dose Estradiol and Norethindrone Acetate in Women With Endometriosis-Associated Pain

Actual Study Start Date :

Dec 7, 2017

Actual Primary Completion Date :

Jun 9, 2020

Actual Study Completion Date :

Apr 8, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Relugolix plus E2/NETA (Group A) Relugolix co-administered with E2/NETA for 24 weeks.	Drug: Relugolix Relugolix 40-mg tablet administered orally once daily. Other Names: TAK-385 MVT-601 Drug: Estradiol/norethindrone acetate Capsule containing co-formulated tablet of E2 (1.0 mg)/NETA (0.5 mg) administered orally once daily. Other Names: E2/NETA
Experimental: Relugolix plus Delayed E2/NETA (Group B) Relugolix co-administered with E2/NETA placebo for 12 weeks, followed by relugolix co-administered with E2/NETA for 12 weeks.	Drug: Relugolix Relugolix 40-mg tablet administered orally once daily. Other Names: TAK-385 MVT-601 Drug: Estradiol/norethindrone acetate Capsule containing co-formulated tablet of E2 (1.0 mg)/NETA (0.5 mg) administered orally once daily. Other Names: E2/NETA Drug: Estradiol/norethindrone acetate placebo E2 (0 mg)/NETA (0 mg) placebo capsule administered orally once daily and designed to match the E2/NETA capsule in size, shape, color, and odor.
Placebo Comparator: Placebo (Group C) Relugolix placebo co-administered with E2/NETA placebo for 24 weeks.	Drug: Estradiol/norethindrone acetate placebo E2 (0 mg)/NETA (0 mg) placebo capsule administered orally once daily and designed to match the E2/NETA capsule in size, shape, color, and odor. Drug: Relugolix placebo Relugolix (0 mg) placebo tablet administered orally once daily and manufactured to match the relugolix tablet in size, shape, color, and odor.

Arm

Intervention/Treatment

Experimental: Relugolix plus E2/NETA (Group A)

Relugolix co-administered with E2/NETA for 24 weeks.

Drug: Relugolix

Relugolix 40-mg tablet administered orally once daily.

Other Names:

TAK-385

MVT-601

Drug: Estradiol/norethindrone acetate

Capsule containing co-formulated tablet of E2 (1.0 mg)/NETA (0.5 mg) administered orally once daily.

Other Names:

E2/NETA

Experimental: Relugolix plus Delayed E2/NETA (Group B)

Relugolix co-administered with E2/NETA placebo for 12 weeks, followed by relugolix co-administered with E2/NETA for 12 weeks.

Drug: Relugolix

Relugolix 40-mg tablet administered orally once daily.

Other Names:

TAK-385

MVT-601

Drug: Estradiol/norethindrone acetate

Capsule containing co-formulated tablet of E2 (1.0 mg)/NETA (0.5 mg) administered orally once daily.

Other Names:

E2/NETA

Drug: Estradiol/norethindrone acetate placebo

E2 (0 mg)/NETA (0 mg) placebo capsule administered orally once daily and designed to match the E2/NETA capsule in size, shape, color, and odor.

Placebo Comparator: Placebo (Group C)

Relugolix placebo co-administered with E2/NETA placebo for 24 weeks.

Drug: Estradiol/norethindrone acetate placebo

E2 (0 mg)/NETA (0 mg) placebo capsule administered orally once daily and designed to match the E2/NETA capsule in size, shape, color, and odor.

Drug: Relugolix placebo

Relugolix (0 mg) placebo tablet administered orally once daily and manufactured to match the relugolix tablet in size, shape, color, and odor.

Outcome Measures

Primary Outcome Measures

Percentage Of Participants Who Meet The Dysmenorrhea Responder Criteria At Week 24 Or End Of Treatment (EOT) [Week 24 or EOT]
Assessed using a Numerical Rating Scale (NRS) score (11-point scale) for pain recorded daily in an electronic diary (e-Diary). The criteria for a responder was based on a pre-defined threshold and accounted for analgesic use.
Percentage Of Participants Who Meet The Non-Menstrual Pelvic Pain (NMPP) Responder Criteria At Week 24 Or EOT [Week 24 or EOT]
Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary. The criteria for a responder was based on a pre-defined threshold and accounted for analgesic use.

Secondary Outcome Measures

Change From Baseline In The Endometriosis Health Profile (EHP)-30 Pain Score At Week 24 [Baseline, Week 24]
Assessed using the Pain Domain of the EHP-30 questionnaire.
Change From Baseline In Dysmenorrhea NRS Score At Week 24 Or EOT [Baseline, Week 24 or EOT]
Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary.
Change From Baseline In NMPP NRS Score At Week 24 Or EOT [Baseline, Week 24 or EOT]
Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary.
Change From Baseline In Overall Pelvic Pain NRS Score At Week 24 Or EOT [Baseline, Week 24 or EOT]
Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary.
Percentage Of Participants Who Are Not Using Opioids For Endometriosis-associated Pain At Week 24 Or EOT [Week 24 or EOT]
Assessed based on usage of protocol-specified opioids for endometriosis-associated pain recorded daily in an e-Diary.
Change From Baseline In Dyspareunia NRS Scores At Week 24 Or EOT [Baseline, Week 24 or EOT]
Assessed using an NRS score (11-point scale) for dyspareunia recorded daily in an e-Diary.
Change From Baseline In Analgesic Use For Endometriosis-associated Pain Based On Mean Pill Count At Week 24 Or EOT [Baseline, Week 24 or EOT]
Assessed based on usage of protocol-specified analgesic for endometriosis-associated pain recorded daily in an e-Diary.
Percentage Of Participants Who Have A Reduction Of At Least 20 Points In The EHP-30 Pain Domain From Baseline To Week 24 [Baseline to Week 24]
Assessed using the pain domain of the EHP-30 questionnaire.
Dysmenorrhea Responder Rate By Month [Baseline to Week 24]
The criteria for a responder was based on a pre-defined threshold and accounted for analgesic use.
NMPP Responder Rate By Month [Baseline to Week 24]
The criteria for a responder was based on a pre-defined threshold and accounted for analgesic use.
Change In Dysmenorrhea NRS Score By Month [Baseline to Week 24]
Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary.
Change In NMPP NRS Score By Month [Baseline to Week 24]
Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary.
Change In Overall Pelvic Pain NRS Score By Month [Baseline to Week 24]
Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary.
Change In Dyspareunia NRS Score By Month [Baseline to Week 24]
Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary.
Change From Baseline In Ibuprofen Use At Week 24 Or EOT [Baseline, Week 24 or EOT]
Assessed using ibuprofen pill counts for endometriosis-associated pain recorded daily in an e-Diary.
Change From Baseline In Opioid Use At Week 24 Or EOT [Baseline, Week 24 or EOT]
Assessed using opioid pill counts for endometriosis-associated pain recorded daily in an e-Diary.
Change From Baseline In The Mean Dysmenorrhea Functional Impairment At Week 24 Or EOT [Baseline, Week 24 or EOT]
Assessed using the subject modified Biberoglu and Behrman 5-point scale for dysmenorrhea recorded daily in an e-Diary.
Change From Baseline In The Mean NMPP Functional Impairment At Week 24 Or EOT [Baseline, Week 24 or EOT]
Assessed using the subject modified Biberoglu and Behrman 4-point scale for pelvic pain recorded daily in an e-Diary.
Change From Baseline In The Mean Dyspareunia Functional Impairment At Week 24 Or EOT [Baseline, Week 24 or EOT]
Assessed using the subject modified Biberoglu and Behrman 5-point scale for dyspareunia recorded daily in an e-Diary.
Change From Baseline In Patient Global Assessment (PGA) For Dysmenorrhea Symptom Severity At Week 24 [Baseline, Week 24]
The PGA for dysmenorrhea is a 1-item questionnaire designed to assess participants' impression of the severity of pain during their menstrual cycle.
Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA For Dysmenorrhea At Week 24 [Week 24]
The PGA for dysmenorrhea is a 1-item questionnaire designed to assess participants' impression of the severity of pain during their menstrual cycle.
Change From Baseline In PGA For NMPP Symptom Severity At Week 24 [Baseline, Week 24]
The PGA for NMPP is a 1-item questionnaire designed to assess participants' impression of the severity of pain when they are not menstruating.
Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA For NMPP At Week 24 [Week 24]
The PGA for NMPP is a 1-item questionnaire designed to assess participants' impression of the severity of pain when they are not menstruating.
Change From Baseline In PGA For Pain Severity At Week 24 [Baseline, Week 24]
The PGA for pain severity is a 1-item questionnaire designed to assess participants' impression of how their pain affected their usual activities.
Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA For Pain Severity At Week 24 [Week 24]
The PGA for pain severity is a 1-item questionnaire designed to assess participants' impression of how their pain affected their usual activities.
Change From Baseline In PGA For Function At Week 24 [Baseline, Week 24]
The PGA for function is a 1-item questionnaire designed to assess participants' impression of how their pain affected their usual activities.
Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA For Function At Week 24 [Week 24]
The PGA for function is a 1-item questionnaire designed to assess participants' impression of how their pain affected their usual activities.
Percentage Of Participants Who Are "Better" Or "Much Better" On The Patient Global Impression Of Change (PGIC) For Dysmenorrhea At Week 24 [Week 24]
The PGIC for dysmenorrhea is a 1-item questionnaire designed to assess participants' impression of change in the severity of pain during their menstrual cycle.
Percentage Of Participants Who Are "Better" Or "Much Better" On The PGIC For NMPP At Week 24 [Week 24]
The PGIC for NMPP is a 1-item questionnaire designed to assess participants' impression of change in the severity of pain during their menstrual cycle.
Percentage Of Participants Who Are "Better" Or "Much Better" On The PGIC For Dyspareunia At Week 24 [Week 24]
The PGIC for dyspareunia is a 1-item questionnaire designed to assess participants' impression of change in the severity of pain during sexual intercourse.
Change From Baseline In The Non-Pain Of The EHP-30 Domains At Week 24 [Baseline, Week 24]
Assessed using the non-pain domains (Control and Powerlessness, Social Support, Emotional Well-Being, and Self-Image) of the EHP-30 questionnaire.
Change From Baseline In The EHP-30 Scale Total Score At Week 24 [Baseline, Week 24]
Assessed using the total score of the EHP-30 questionnaire.
Change From Baseline In The EHP Work Domain Score At Week 24 [Baseline, Week 24]
The EHP Work domain is a 5-item questionnaire that assesses impact of pain on ability to work.
Categorical Change From Baseline In Quality Of Life Assessed By European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Questionnaire At Week 24 [Baseline, Week 24]
The EQ-5D-5L is a 5-item questionnaire designed to assess quality of life.
Change From Baseline To Week 24 In EQ-5D-5L Visual Analogue Scale Score At Week 24 [Baseline, Week 24]
The EQ-5D-5L is a 5-item questionnaire designed to assess quality of life.
Percentage Of Participants Who Meet The Dysmenorrhea Responder Criteria At Week 24 Or EOT For Relugolix Plus Delayed E2/NETA [Week 24 or EOT]
Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary. The criteria for a responder was based on a pre-defined threshold and accounted for analgesic use.
Percentage Of Participants Who Meet The NMPP Responder Criteria At Week 24 Or EOT For Relugolix Plus Delayed E2/NETA [Week 24 or EOT]
Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary. The criteria for a responder was based on a pre-defined threshold and accounted for analgesic use.
Change From Baseline In The EHP-30 Pain Score At Week 24 For Relugolix Plus Delayed E2/NETA [Baseline, Week 24]
Assessed using the Pain Domain of the EHP-30 questionnaire.
Percentage Of Participants Who Have A Reduction Of At Least 20 Points In The EHP-30 Pain Domain From Baseline To Week 24 For Relugolix Plus Delayed E2/NETA [Baseline to Week 24]
Assessed using the pain domain of the EHP-30 questionnaire.
Percentage Change From Baseline In Bone Mineral Density At The Lumbar Spine (L1-L4) At Week 12 [Baseline, Week 12]
Assessed by dual-energy X-ray absorptiometry (DXA) scan.
Percentage Change From Baseline In Bone Mineral Density At Lumbar Spine (L1-L4), Femoral Neck, And Total Hip At Week 24 [Baseline, Week 24]
Assessed by DXA scan.
Percentage Of Participants Experiencing Vasomotor Symptoms At Week 12 Between Group A And B [Week 12]
Change From Baseline In Serum Concentrations Of Luteinizing Hormone, Follicle Stimulating Hormone, Estradiol, And Progesterone [Baseline, Week 24]
Blood samples will be collected from participants for hormonal measurements.
Pre-dose Relugolix Plasma Concentrations [Week 4]
Blood samples will be collected from participants for relugolix measurements.
Endometrial Biopsy At Week 24 [Week 24]
Primary diagnosis of endometrial biopsy assessment by pathologist.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Is a premenopausal female aged 18 to 50 years old (inclusive) on the day of signing of the informed consent form.
Has agreed to use only study-specified analgesic medications during the study and is not known to be intolerant to these.
Has a diagnosis of endometriosis and has had, within 10 years prior to signing the informed consent form, surgical or direct visualization and/or histopathologic confirmation of endometriosis, for example, during a laparoscopy or laparotomy.
During the Run-In Period (35 to 70 days prior to treatment period) has a dysmenorrhea NRS score ≥ 4.0 on at least 2 days and
Mean NMPP NRS score ≥ 2.5, or
Mean NMPP NRS score ≥ 1.25 and NMPP NRS score ≥ 5.0 on ≥ 4 days.

Key Exclusion Criteria:

Has a history of chronic pelvic pain that is not caused by endometriosis.
Has any chronic pain or frequently recurring pain condition, other than endometriosis that is treated with opioids or requires analgesics for ≥ 7 days per month.
Has had surgical procedures for treatment of endometriosis within the 3 months prior to the Screening visit.
Has a history of or currently has osteoporosis or other metabolic bone disease.
Has a clinically significant gynecologic condition, other than endometriosis, identified during Screening or Run-In period transvaginal ultrasound or endometrial biopsy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dothan	Dothan	Alabama	United States	36303
2	Mesa	Mesa	Arizona	United States	85209
3	Scottsdale	Scottsdale	Arizona	United States	85251
4	Tucson	Tucson	Arizona	United States	85704
5	Tucson	Tucson	Arizona	United States	85712
6	Canoga Park	Canoga Park	California	United States	91303
7	Long Beach	Long Beach	California	United States	90806
8	San Diego	San Diego	California	United States	92111
9	Greenwood Village	Greenwood Village	Colorado	United States	80111
10	Fort Myers	Fort Myers	Florida	United States	33912
11	Loxahatchee	Loxahatchee Groves	Florida	United States	33470
12	Miami	Miami	Florida	United States	33126
13	Miami	Miami	Florida	United States	33155
14	Orlando	Orlando	Florida	United States	32808
15	Oviedo	Oviedo	Florida	United States	32765
16	Plantation	Plantation	Florida	United States	33324
17	Sarasota	Sarasota	Florida	United States	34239
18	Atlanta	Atlanta	Georgia	United States	30363
19	Augusta	Augusta	Georgia	United States	30909
20	Norcross	Norcross	Georgia	United States	30093
21	Idaho Falls	Idaho Falls	Idaho	United States	83404
22	Oakbrook	Oak Brook	Illinois	United States	60523
23	Shawnee	Shawnee Mission	Kansas	United States	66218
24	New Orleans	New Orleans	Louisiana	United States	70115
25	Jefferson City	Jefferson City	Missouri	United States	65109
26	Las Vegas	Las Vegas	Nevada	United States	89113
27	Port Jefferson	Port Jefferson	New York	United States	11777
28	Durham	Durham	North Carolina	United States	27713
29	Raleigh	Raleigh	North Carolina	United States	27612
30	Winston Salem	Winston-Salem	North Carolina	United States	27103
31	Englewood	Englewood	Ohio	United States	45322
32	Hershey	Hershey	Pennsylvania	United States	17033
33	Philadelphia	Philadelphia	Pennsylvania	United States	19104
34	Memphis	Memphis	Tennessee	United States	38120
35	Murfreesboro	Murfreesboro	Tennessee	United States	37130
36	Austin	Austin	Texas	United States	78705
37	Houston	Houston	Texas	United States	77030
38	Webster	Webster	Texas	United States	77598
39	Salt Lake City	Salt Lake City	Utah	United States	84107
40	Salt Lake City	Salt Lake City	Utah	United States	84124
41	Norfolk	Norfolk	Virginia	United States	23507
42	Richmond	Richmond	Virginia	United States	23235
43	Seattle	Seattle	Washington	United States	98105
44	Ciudad de Buenos Aires	Ciudad de Buenos Aires	Buenos Aires	Argentina	C1128AAF
45	San Isidro	San Isidro	Buenos Aires	Argentina	B1642CKL
46	Rosario	Rosario	Santa Fe	Argentina	S2000PRB
47	Córdoba	Córdoba		Argentina	X5000JHQ
48	Leuven	Leuven	Flemish Brabant	Belgium	3000
49	La Louvière	La Louvière	Hainaut	Belgium	7100
50	Gent	Gent	Oost-vlaanderen	Belgium	9000
51	Brussels	Brussels		Belgium	1070
52	Sofia	Sofia	Sofiya	Bulgaria	1233
53	Sofia	Sofia	Sofiya	Bulgaria	1431
54	Sofia	Sofia	Sofiya	Bulgaria	1504
55	Blagoevgrad	Blagoevgrad		Bulgaria	2700
56	Pleven	Pleven		Bulgaria	5809
57	Sofia	Sofia		Bulgaria	1336
58	Sofia	Sofia		Bulgaria	1606
59	Stara Zagora	Stara Zagora		Bulgaria	6003
60	Varna	Varna		Bulgaria	9005
61	Red Deer	Red Deer	Alberta	Canada	T4N 6V7
62	Waterloo	Waterloo	Ontario	Canada	N2J1C4
63	Victoriaville	Victoriaville	Quebec	Canada	G6P 6P6
64	Praha 10	Praha 10	Praha	Czechia	100 34
65	Nachod	Náchod		Czechia	54701
66	Olomouc	Olomouc		Czechia	772 00
67	Praha 8 - Libeň	Praha 8 - Libeň		Czechia	180 81
68	Vodnany	Vodňany		Czechia	389 01
69	Vysoké Mýto	Vysoké Mýto		Czechia	566 01
70	Kuopio	Kuopio	Eastern Finland	Finland	FI-70110
71	Helsinki	Helsinki	Southern Finland	Finland	00260
72	Oulu	Oulu		Finland	90100
73	Kecskemét	Kecskemét	Bacs-kiskun	Hungary	6000
74	Pécs	Pécs	Baranya	Hungary	7624
75	Békéscsaba	Békéscsaba	Bekes	Hungary	5600
76	Gyula	Gyula	Bekes	Hungary	5700
77	Szeged	Szeged	Csongrad	Hungary	6725
78	Debrecen	Debrecen	Hajdu-bihar	Hungary	4024
79	Debrecen	Debrecen	Hajdu-bihar	Hungary	4025
80	Debrecen	Debrecen	Hajdu-Bihar	Hungary	4032
81	Nyíregyháza	Nyíregyháza	Szabolcs-szatmar-bereg	Hungary	4400
82	Budapest	Budapest		Hungary	1027
83	Budapest	Budapest		Hungary	1062
84	Budapest	Budapest		Hungary	1135
85	Lódz	Lódz	Lodzkie	Poland	90-602
86	Lublin	Lublin	Lubelskie	Poland	20-064
87	Lublin	Lublin	Lubelskie	Poland	20-632
88	Lublin	Lublin	Lubelskie	Poland	20-880
89	Kraków	Kraków	Malopolskie	Poland	31-121
90	Warszawa	Warszawa	Mazowieckie	Poland	02-066
91	Warszawa	Warszawa	Mazowieckie	Poland	02-929
92	Białystok	Białystok	Podlaskie	Poland	15-224
93	Katowice	Katowice	Slaskie	Poland	02-066
94	Katowice	Katowice	Slaskie	Poland	40-081
95	Poznań	Poznań	Wielkopolskie	Poland	60-535
96	Skórzewo	Skórzewo	Wielkopolskie	Poland	601-85
97	Szczecin	Szczecin	Zachodniopomorskie	Poland	71-434
98	Almada	Almada	Lisboa	Portugal	2805-267
99	Coimbra	Coimbra		Portugal	3000-075
100	Covilhã	Covilhã		Portugal	6200-251
101	Lisbon	Lisbon		Portugal	1069-089
102	Porto	Porto		Portugal	4099-001
103	Port Elizabeth	Port Elizabeth	Eastern Cape	South Africa	6001
104	Centurion	Centurion	Gauteng	South Africa	0157
105	Roodepoort	Roodepoort	Gauteng	South Africa	1724
106	Durban	Durban	Kwazulu-natal	South Africa	4001
107	Cape Town	Cape Town	Western Cape	South Africa	7405
108	Madrid	Madrid		Spain	28041
109	Valencia	Valencia		Spain	46010
110	Kyiv	Kyiv	Kiev City	Ukraine	02232
111	Kyiv	Kyiv	Kiev City	Ukraine	04050
112	Kyiv	Kyiv	Kiev	Ukraine	01034
113	Chernivtsi	Chernivtsi		Ukraine	58001
114	Ivano-Frankivsk	Ivano-Frankivsk		Ukraine	76018
115	Kharkiv	Kharkiv		Ukraine	61052
116	Kiev	Kiev		Ukraine	03148
117	Kiev	Kiev		Ukraine	04053
118	Kiev	Kiev		Ukraine	04112
119	Vinnytsya	Vinnytsya		Ukraine	21101
120	Zaporizhzhya	Zaporizhzhya		Ukraine	69065
121	Zaporizhzhya	Zaporizhzhya		Ukraine	69068
122	Zaporizhzhya	Zaporizhzhya		Ukraine	69071
123	Zaporizhzhya	Zaporizhzhya		Ukraine	69663