Debut: Flexible-dose, Long-term Safety Study of Lu AF35700 in Adult Patients With Schizophrenia

• Sponsor: H. Lundbeck A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02892422
• Collaborator: (none)
• Enrollment: 528
• Locations: 102
• Arm: 1
• Actual Duration (Months): 38.3
• Patients Per Site: 5.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

To evaluate the safety and tolerability of the long-term treatment with Lu AF35700.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: Lu AF35700	Phase 3

Detailed Description

Safety study in patients with schizophrenia who have participated and completed a study investigating Lu AF35700 including Studies 16159A and 16323A. Or in patients with schizophrenia for whom a switch of antipsychotic treatment can be potentially beneficial according to the investigator's clinical judgement.

Study Design

• Study Type: Interventional
• Actual Enrollment: 528 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Interventional, Open-label, Flexible-dose, Long-term Safety Study of Lu AF35700 in Adult Patients With Schizophrenia
• Actual Study Start Date: Aug 1, 2016
• Actual Primary Completion Date: Oct 10, 2019
• Actual Study Completion Date: Oct 10, 2019

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Flexible-dose of Lu AF35700

Drug: Lu AF35700; Flexible-dose of Lu AF35700, 10 or 20 mg/day, tablets, orally. From Day 8, the daily dose can be increased to 20mg. Thereafter, the daily dose can be adjusted (decreased to 10mg or following a decrease, increased to 20mg/day) Patients who completed the 16159A study, only, can be switched to a weekly 70 mg Lu AF35700 dosing regimen (tablets, orally, once weekly) after 8 weeks in this study

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Treatment-Emergent Adverse Events (Safety and Tolerability) [From dosing to end of study (57 weeks)]

   Based on the safety assessments (e.g. clinical safety laboratory tests, vital signs, weight, waist circumference and ECG)

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• For 16159A-patients

• The patient has completed Study 16159A.

• The patient is able to read and understand the Informed Consent Form.

• The patient has signed the Informed Consent Form specific for Study 16159B.

• The patient can potentially benefit from 52-week treatment with Lu AF35700 according to the investigator's clinical judgement.

For 16323A-patients

• The patient has completed the dosing period of Study 16323A.

• The patient is able to read and understand the Informed Consent Form.

• The patient has signed the Informed Consent Form specific Study 16159B.

• The patient has a confirmed diagnosis of schizophrenia according to DSM-5™.

• The patient can potentially benefit from 52-week treatment with Lu AF35700 according to the investigator's clinical judgement.

For Other Patients

• The patient has schizophrenia, diagnosed according to DSM-5™.

• The patient is a man or woman, aged ≥18 years.

• The patient has been prescribed oral antipsychotic treatment at the recommended dose range as stated in the summary of product characteristics or equivalent label for 6 weeks prior to the Screening Visit.

• The patient has a PANSS total score ≥60 and ≤90 at Screening and Baseline Visits.

• The patient has a Clinical Global Impression - Severity of Illness (CGI-S) score ≤4.

• The patient is in need of a change in the current antipsychotic treatment and, according to the investigator's clinical judgement, the patient can potentially benefit from a switch to another treatment including, but not limited to, any of the following reasons:

• lack of adequate response to his or her current antipsychotic medication;

• poor tolerability to his or her current antipsychotic medication;

• unwillingness of the patient to adhere to his or her current antipsychotic medication.

Exclusion Criteria:

• For 16159A-patients

• The patient has been diagnosed with a primary psychiatric disorder other than schizophrenia during Study 16159A.

• The patient, in the opinion of the investigator, is at significant risk of suicide, or: Answers "Yes" to any question on the Suicidal Behaviour section of the Columbia-Suicide Severity Rating Scale (C-SSRS), OR Answers "Yes" to questions 4 and 5 on the Suicidal Ideation section of the C-SSRS

For 16323A-patients

• The patient has been diagnosed with a primary psychiatric disorder other than schizophrenia during Study 16323A.

• The patient, in the opinion of the investigator, is at significant risk of suicide, or: Answers "Yes" to any question on the Suicidal Behaviour section of the C-SSRS, OR Answers "Yes" to questions 4 and 5 on the Suicidal Ideation section of the C-SSRS

For Other Patients

• The patient has any current psychiatric disorder (DSM-5™ criteria) other than schizophrenia established as the primary diagnosis.

• The patient is experiencing acute exacerbation of psychotic symptoms at the Screening Visit, between the Screening and Baseline Visits or at the Baseline Visit.

• The patient is treated with clozapine at the time of the Screening Visit.

• The patient has a substance use disorder (except nicotine) which according to the investigator's judgment may compromise the patient's ability to comply with the study procedures, or preclude the benefits of the study medication.

• The patient, in the opinion of the investigator, is at significant risk of suicide, or: Answers "Yes" to any question on the Suicidal Behaviour section of the C-SSRS, OR Answers "Yes" to questions 4 and 5 on the Suicidal Ideation section of the C-SSRS

Other protocol defined inclusion and exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	US1018	Bellflower	California	United States
2	US1062	Costa Mesa	California	United States	92626
3	US1463	Culver City	California	United States
4	US1399	Escondido	California	United States	91945
5	US1104	Garden Grove	California	United States	92845
6	US1114	National City	California	United States	91950
7	US1459	Oceanside	California	United States
8	US1368	Orange	California	United States	92868
9	US1391	San Bernardino	California	United States	92408-3332
10	US1392	Torrance	California	United States	90502-4432
11	US1318	Lauderhill	Florida	United States	33319
12	US1130	Miami	Florida	United States	33122
13	US1129	North Miami	Florida	United States	33161-5834
14	US1402	Oakland Park	Florida	United States	33334-4400
15	US1403	Atlanta	Georgia	United States	30328
16	US1009	Atlanta	Georgia	United States	30331
17	US1046	Chicago	Illinois	United States	60640
18	US1423	Hoffman Estates	Illinois	United States	60169-1067
19	US1398	Shreveport	Louisiana	United States	71101-4603
20	US1404	Shreveport	Louisiana	United States	71104-2136
21	US1086	Flowood	Mississippi	United States	39232
22	US1444	Las Vegas	Nevada	United States	89102-1943
23	US1426	Berlin	New Jersey	United States	08009
24	US1244	Fresh Meadows	New York	United States	11432
25	US1394	New York	New York	United States	10032
26	US1416	New York	New York	United States	10035-6000
27	US1171	Rochester	New York	United States	14618
28	US1190	Staten Island	New York	United States	10312-6501
29	US1390	Charlotte	North Carolina	United States	28204-3110
30	US1124	Norristown	Pennsylvania	United States	19403
31	US1451	Austin	Texas	United States	78754-5122
32	US1065	Dallas	Texas	United States	75243
33	BG1030	Burgas		Bulgaria
34	BG1028	Kazanlak		Bulgaria
35	BG1003	Lovech		Bulgaria
36	BG1008	Plovdiv		Bulgaria
37	BG1024	Sofia		Bulgaria
38	BG1026	Sofia		Bulgaria
39	BG1034	Varna		Bulgaria
40	BG1029	Veliko Tŭrnovo		Bulgaria
41	BG1027	Vratsa		Bulgaria
42	CA1029	Penticton		Canada
43	CZ1023	Brno		Czechia
44	CZ1032	Brno		Czechia
45	CZ1013	Lnáře		Czechia
46	CZ1038	Praha		Czechia
47	EE1007	Tallinn		Estonia
48	MX1024	Durango		Mexico
49	MX1011	Guadalajara		Mexico
50	MX1021	Guadalajara		Mexico
51	MX1022	Guadalajara		Mexico
52	MX1020	Mexico City		Mexico
53	MX1005	Monterrey		Mexico
54	MX1007	Monterrey		Mexico
55	MX1015	Monterrey		Mexico
56	PL1043	Bialystok		Poland
57	PL1058	Pruszcz Gdanski		Poland
58	PL1059	Toruń		Poland
59	PL1051	Wrocław		Poland
60	PL1060	Łódź		Poland
61	RO1024	Bucharest		Romania
62	RU1009	Arkhangel'sk		Russian Federation
63	RU1021	Gatchina		Russian Federation
64	RU1006	Moscow		Russian Federation
65	RU1051	Moscow		Russian Federation
66	RU1055	Moscow		Russian Federation
67	RU1053	Roshchino		Russian Federation
68	RU1023	Saint Petersburg		Russian Federation
69	RU1028	Saint Petersburg		Russian Federation
70	RU1030	Saint Petersburg		Russian Federation
71	RU1031	Saint Petersburg		Russian Federation
72	RU1049	Saint Petersburg		Russian Federation
73	RU1052	Saint Petersburg		Russian Federation
74	RU1056	Saint Petersburg		Russian Federation
75	RU1050	Yaroslavl		Russian Federation
76	RS1008	Belgrade		Serbia
77	RS1010	Belgrade		Serbia
78	RS1012	Belgrad		Serbia
79	RS1001	Kovin		Serbia
80	RS1011	Kragujevac		Serbia
81	RS1016	Kragujevac		Serbia
82	RS1017	Kragujevac		Serbia
83	RS1009	Novi Kneževac		Serbia
84	SK1014	Bratislava		Slovakia
85	SK1024	Bratislava		Slovakia
86	SK1026	Zlaté Moravce		Slovakia
87	ES1047	Barcelona		Spain
88	ES1008	Málaga		Spain
89	ES1048	Oviedo		Spain
90	UA1017	Kharkiv		Ukraine
91	UA1035	Kharkiv		Ukraine
92	UA1029	Kherson		Ukraine
93	UA1027	Kiev		Ukraine
94	UA1028	Kiev		Ukraine
95	UA1030	Kiev		Ukraine
96	UA1031	Kiev		Ukraine
97	UA1033	Lviv		Ukraine
98	UA1020	Odesa		Ukraine
99	UA1019	Odessa		Ukraine
100	UA1032	Oleksandrivka		Ukraine
101	UA1001	Poltava		Ukraine
102	UA1036	Vinnitsa		Ukraine

Sponsors and Collaborators

• H. Lundbeck A/S

Investigators

• Study Director: Email contact via H. Lundbeck A/S, [e-mail]

Study Documents (Full-Text)

• Study Protocol - May 24, 2016
• Statistical Analysis Plan - Nov 5, 2019

More Information

Publications

None provided.

• Responsible Party: H. Lundbeck A/S
• ClinicalTrials.gov Identifier: NCT02892422
• Other Study ID Numbers: 16159B; 2015-003284-11
• First Posted: Sep 8, 2016
• Last Update Posted: Oct 26, 2020
• Last Verified: Sep 1, 2020

• Additional relevant MeSH terms: Schizophrenia

Study Results

Participant Flow

Pre-assignment Detail	Participants who had completed either study 16159A or 16323A were enrolled. Participants from study 16323A were excluded from the "all patients treated dataset" and from the "full analysis dataset".

Arm/Group Title	Lu AF35700 Flexible-dose
Arm/Group Description	Lu AF35700: Flexible-dose of Lu AF35700, 10 or 20 mg/day, tablets, orally. From Day 8, the daily dose can be increased to 20mg. Thereafter, the daily dose can be adjusted (decreased to 10mg or following a decrease, increased to 20mg/day) Patients who completed the 16159A study, only, can be switched to a weekly 70 mg Lu AF35700 dosing regimen (tablets, orally, once weekly) after 8 weeks in this study
Period Title: Overall Study
STARTED	528
COMPLETED	318
NOT COMPLETED	210

Baseline Characteristics

Arm/Group Title	Flexible-dose of Lu AF35700
Arm/Group Description	Lu AF35700: Flexible-dose of Lu AF35700, 10 or 20 mg/day, tablets, orally. From Day 8, the daily dose can be increased to 20mg. Thereafter, the daily dose can be adjusted (decreased to 10mg or following a decrease, increased to 20mg/day) Patients who completed the 16159A study, only, can be switched to a weekly 70 mg Lu AF35700 dosing regimen (tablets, orally, once weekly) after 8 weeks in this study
Overall Participants	528
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.3 (11.67)
Sex: Female, Male (Count of Participants)
Female	220 41.7%
Male	308 58.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.2%
Asian	1 0.2%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	63 11.9%
White	412 78%
More than one race	0 0%
Unknown or Not Reported	51 9.7%
Region of Enrollment (participants) [Number]
Romania	3 0.6%
United States	98 18.6%
Czechia	11 2.1%
Ukraine	48 9.1%
Russia	112 21.2%
Spain	3 0.6%
Canada	3 0.6%
Poland	19 3.6%
Mexico	57 10.8%
Slovakia	8 1.5%
Bulgaria	107 20.3%
Serbia	43 8.1%
Estonia	16 3%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (Safety and Tolerability)
Description	Based on the safety assessments (e.g. clinical safety laboratory tests, vital signs, weight, waist circumference and ECG)
Time Frame	From dosing to end of study (57 weeks)

Outcome Measure Data

Analysis Population Description

Participants from study 16323A were excluded from the "all patients treated dataset" and from the "full analysis dataset".

Arm/Group Title	Flexible-dose of Lu AF35700
Arm/Group Description	Lu AF35700: Flexible-dose of Lu AF35700, 10 or 20 mg/day, tablets, orally. From Day 8, the daily dose can be increased to 20mg. Thereafter, the daily dose can be adjusted (decreased to 10mg or following a decrease, increased to 20mg/day) Patients who completed the 16159A study, only, can be switched to a weekly 70 mg Lu AF35700 dosing regimen (tablets, orally, once weekly) after 8 weeks in this study
Measure Participants	524
Count of Participants [Participants]	289 54.7%

Adverse Events

Time Frame	57 weeks
Arm/Group Title	Lu AF35700 Flexible-dose
Arm/Group Description	Lu AF35700: Flexible-dose of Lu AF35700, 10 or 20 mg/day, tablets, orally.
All Cause Mortality
	Lu AF35700 Flexible-dose
	Affected / at Risk (%)	# Events
Total	0/524 (0%)
Serious Adverse Events
	Lu AF35700 Flexible-dose
	Affected / at Risk (%)	# Events
Total	28/524 (5.3%)
Cardiac disorders
Acute myocardial infarction	1/524 (0.2%)	1
Injury, poisoning and procedural complications
Hip fracture	1/524 (0.2%)	1
Intentional overdose	2/524 (0.4%)	2
Nervous system disorders
Coma	1/524 (0.2%)	1
Parkinsonism	1/524 (0.2%)	1
Psychiatric disorders
Acute psychosis	1/524 (0.2%)	1
Alcohol withdrawal syndrome	1/524 (0.2%)	1
Disinhibition	1/524 (0.2%)	1
Hallucination, auditory	1/524 (0.2%)	1
Insomnia	1/524 (0.2%)	1
Psychotic disorder	3/524 (0.6%)	3
Schizophrenia	16/524 (3.1%)	19
Suicide attempt	2/524 (0.4%)	2
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/524 (0.2%)	1
Other (Not Including Serious) Adverse Events
	Lu AF35700 Flexible-dose
	Affected / at Risk (%)	# Events
Total	43/524 (8.2%)
Nervous system disorders
Headache	43/524 (8.2%)	49

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.