A Study to Test the Effect of Different Doses of BI 1358894 and Quetiapine in People With Depression

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04521478
• Collaborator: (none)
• Enrollment: 431
• Locations: 84
• Arms: 3
• Anticipated Duration (Months): 38.8
• Patients Per Site: 5.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study is open to adults with depression (major depressive disorder) for whom standard treatment with antidepressants alone does not work sufficiently. The purpose of the trial is to find out whether a medicine called BI 1358894 helps to improve symptoms of depression. Four different doses of BI 1358894 are tested in the study. Participants continue their standard antidepressant therapy throughout the study.

Participants are put into 6 groups by chance. Participants in 4 of the 6 groups take different doses of BI 1358894, and placebo. Participants in the fifth group take quetiapine, a medicine already used to treat depression, and placebo. Participants in the sixth group take placebo only.

Participants take BI 1358894, quetiapine, or placebo as tablets twice a day. Placebo tablets look like BI 1358894 or quetiapine tablets but do not contain any medicine.

Participants are in the study for about 3 months. During this time, they visit the study site about 8 times and get about 2 phone calls. At the visits, doctors ask participants about their symptoms.

The results between the BI 1358894 groups, the quetiapine group, and the placebo group are then compared. The doctors also regularly check the general health of the participants.

Condition or Disease	Intervention/Treatment	Phase
Depressive Disorder, Major	Drug: BI 1358894; Drug: Placebo; Drug: Quetiapine	Phase 2

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 431 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase II, 6-week, Multicenter, Randomized, Double-blind, Double-dummy, Placebo-controlled, Parallel Group Trial With a Quetiapine Arm to Evaluate the Efficacy, Tolerability and Safety of Oral BI 1358894 in Patients With Major Depressive Disorder With Inadequate Response to Antidepressants
• Actual Study Start Date: Nov 20, 2020
• Anticipated Primary Completion Date: Jan 16, 2024
• Anticipated Study Completion Date: Feb 15, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment group 1 BI 1358894	Drug: BI 1358894; BI 1358894
Placebo Comparator: Placebo group Placebo	Drug: Placebo; Placebo
Experimental: Treatment group 2 Quetiapine	Drug: Quetiapine; quetiapine

Outcome Measures

Primary Outcome Measures

1. Change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) total score [At week 6]

   The MADRS consists of 10 items: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thought, suicidal thoughts. MADRS items are rated on a 0-6 continuum (0=no abnormality, 6=severe). The possible total score could range from 0 to 60 (from normal with absence of symptoms to severe depression).

Secondary Outcome Measures

1. Response defined as ≥ 50% MADRS reduction from baseline [At week 6]

2. Change from baseline in State-Trait Anxiety Inventory (STAI) State and Trait version scores [At week 6]

   The S-Anxiety scale (STAI Form Y-1) consists of twenty statements that evaluate how respondents feel "right now, at this moment." The T-Anxiety scale (STAI Form Y-2) consists of twenty statements that assess how people generally feel. Each STAI item is given a weighted score of 1 to 4. A rating of 4 indicates the presence of a high level of anxiety for ten S-Anxiety items and eleven T-Anxiety items (e.g., "I feel frightened," "I feel upset"). A high rating indicates the absence of anxiety for the remaining ten S-Anxiety items and nine T-Anxiety items (e.g., "I feel calm," "I feel relaxed").Scores for both the S-Anxiety and the T-Anxiety scales can vary from a minimum of 20 to a maximum of 80. Higher scores indicate greater anxiety.

3. Change from baseline in Clinical Global Impression Severity Scale (CGI-S) score [At week 6]

   The CGI-S evaluates the severity of psychopathology on a scale of 1 to 7. Considering total clinical experience with the depression population, a participant is assessed on severity of illness at the time of rating according to: 1=normal (not at all ill); 2=borderline ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill participants. Higher scores indicate worsening.

4. Change from baseline in Symptoms of Major Depressive Disorder Scale (SMDDS) total score [At week 6]

   The different categories and associated 16 items are: Negative Emotions/Mood: sadness, hopeless/helpless, irritability, anhedonia; Anxiety: feeling overwhelmed, worry; Low Energy: tiredness; Cognition: intrusive thoughts, poor concentration; Sleep Disturbances: general sleep adequacy; Self Harm/Suicide: life not worth living; Low Motivation: lack of drive, no interest in activities; Sense of Self: self-blame; Eating Behavior: poor appetite, overeating. The SMDDS uses a recall of "over the past 7 days" and participants respond to each question using a rating scale between 0 ("Not at all" or "Never") to 4 ("Extremely" or "Always"). The total score ranges from 0 to 60 with a higher score indicating more severe depressive symptomatology.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

--Established diagnosis of Major Depressive Disorder (MDD), single episode or recurrent, as confirmed at the time of screening by the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 5th version (DSM-5) (SCID-5), with a duration of current depressive episode ≥ 8 weeks and ≤ 18 months at the time of screening visit

• Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≥ 24 at screening, as confirmed by a trained site based rater AND interactive, computer administered MADRS. The difference in the rater and computer administered MADRS must not exceed more than 7 points (for details refer to section 6.2). In addition, trial participants must have a score of ≥ 3 on the Reported Sadness Item on both MADRS scales (computer administered and rater-administered MADRS)

• A documented ongoing monotherapy treatment of ≥ 6 weeks at the screening visit, with a protocol specified Selective Serotonin Reuptake Inhibitor (SSRI) or Serotonin Norepinephrine Reuptake Inhibitor (SNRI) (refer to the ISF) at adequate dose (at least minimum effective dose as per prescribing information and as confirmed per detectable drug levels in the screening blood or urine sampling)

• Male and female participants, 18 to 65 years of age, both inclusively at the time of consent

• Women who are of child-bearing potential (WOCBP)1 must be able and willing to use two methods of contraception which include one highly effective method of birth control per ICH M3 (R2) that result in a low failure rate of less than 1%, plus one additional barrier

• Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial

• Able to communicate well, and to understand and comply with trial requirements

Exclusion Criteria:

• Per DSM-5, had ever met diagnostic criteria for schizophrenia, schizoaffective disorder, schizophreniform disorder, bipolar disorder, delusional disorder or MDD with psychotic features as assessed by the Structured Clinical Interview for DSM-5 Clinical Trials (SCID-5) at the time of screening

• Diagnosis of any other mental disorder (in addition to those as described in Exclusion Criterion #1) that was the primary focus of treatment within 6 months prior to screening or at baseline (as per clinical discretion of the investigator)

• Diagnosis with antisocial, paranoid, schizoid or schizotypal personality disorder as per DSM-5 criteria, at the time of screening visit. Any other personality disorder at screening visit that significantly affects current psychiatric status and likely to impact trial participation, as per the judgement of investigator

• Diagnosis of a substance related disorder within 3 months prior to screening visit (with exception of caffeine and tobacco)

• History of seizure disorders, stroke, brain tumor or any other major neurological illness that can impact participation in the trial

• History of more than 2 unsuccessful monotherapy treatments (at adequate dosage and duration, per local prescribing information of the product) with an approved antidepressant medication for the current ongoing major depressive episode. These include ongoing monotherapy treatment with a protocol specified SSRI or SNRI as described in Inclusion Criterion #3

• Any suicidal behavior in the past 12 months prior to screening (per investigator judgement including an actual attempt, interrupted attempt, aborted attempt, or preparatory acts or behaviour)

• Any suicidal ideation of type 4 or 5 in the Columbia Suicide Severity Rating Scale (CSSRS) in the past 3 months prior to screening or at screening or baseline visit (i.e. active suicidal thought with method and intent but without specific plan, or active suicidal thought with method, intent and plan)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	Collaborative Neuroscience Network, LLC (CNS)	Garden Grove	California	United States	92845
3	California Neuroscience Research	Sherman Oaks	California	United States	91403
4	Schuster Medical Research Institute	Sherman Oaks	California	United States	91403
5	Viking Clinical Research, Ltd.	Temecula	California	United States	92591
6	Collaborative Neuroscience Research	Torrance	California	United States	90502
7	Institute of Living	Hartford	Connecticut	United States	06106
8	Gulf Coast Clinical Research Center	Fort Myers	Florida	United States	33912
9	Sarkis Clinical Trials	Gainesville	Florida	United States	32607
10	Clinical Neuroscience Solutions, Inc	Jacksonville	Florida	United States	32256
11	Atlanta Center	Atlanta	Georgia	United States	30331
12	Psychiatric Medicine Associates, LLC	Skokie	Illinois	United States	60076
13	University of Kansas School of Medicine-Wichita	Wichita	Kansas	United States	67214
14	Precise Research Centers	Flowood	Mississippi	United States	39232
15	Psychiatric Care and Research Center	O'Fallon	Missouri	United States	63368
16	Hassman Research Institute	Marlton	New Jersey	United States	08053
17	Synexus Clinical Research US, Inc.	New York	New York	United States	10017
18	The Ohio State University Wexner Medical Center	Columbus	Ohio	United States	43210
19	Lehigh Center for Clinical Research	Allentown	Pennsylvania	United States	18104
20	Core Clinical Research	Everett	Washington	United States	98201
21	Griffith Health	Southport	Queensland	Australia	4125
22	Peninsula Therapeutic and Research Group	Frankston	Victoria	Australia	3199
23	Monash Alfred Psychiatry Research Centre	Melbourne	Victoria	Australia	3004
24	Neuropsychiatry, s.r.o.	Hradec Kralove		Czechia	500 09
25	Clinical Research Foundation s.r.o	Kladno		Czechia	27201
26	A-SHINE s.r.o	Plzen		Czechia	31200
27	Clintrial s.r.o.	Prague		Czechia	10000
28	AD71 s.r.o.	Prague		Czechia	10900
29	INEP medical s.r.o.	Prague		Czechia	18600
30	HOP Dijon-Bourgogne	Dijon		France	21079
31	CAB Médical Psyché	Douai		France	59500
32	CAB Ambroise Paré	Elancourt		France	78990
33	HOP la Colombière	Montpellier		France	34295
34	HOP Saint-Jacques	Nantes		France	44093
35	HOP Pasteur	Nice		France	06000
36	HOP Carémeau	Nîmes		France	30029
37	HOP Henri Laborit	Poitiers		France	86021
38	CTR Psychiatrique Universitaire	Saint-Cyr-sur-Loire		France	37540
39	HOP Purpan	Toulouse		France	31059
40	Zentrum für klinische Forschung Dr. Schöll, Dr. Steidl & Kollegen	Bad Homburg		Germany	61348
41	Universitätsklinikum Frankfurt	Frankfurt am Main		Germany	60590
42	Universitätsmedizin der Johannes Gutenberg-Universität Mainz	Mainz		Germany	55131
43	Zentralinstitut für seelische Gesundheit	Mannheim		Germany	68159
44	Praxis für Psychiatrie und Psychotherapie	Stralsund		Germany	18439
45	Studienzentrum Nord-West	Westerstede		Germany	26655
46	Obudai Egeszsegugyi Centrum	Budapest		Hungary	1036
47	Semmelweis University	Budapest		Hungary	1083
48	Bugat Pal Hospital, Gyongyos	Gyongyos		Hungary	3200
49	National Center for Global Health and Medicine Kohnodai Hospital	Chiba, Ichikawa		Japan	272-8516
50	Kaku Mental Clinic	Fukuoka, Fukuoka		Japan	810-0022
51	Fukuoka University Hospital	Fukuoka, Fukuoka		Japan	814-0180
52	Kuramitsu Hospital	Fukuoka, Fukuoka		Japan	819-0037
53	Hokudai-dori Mental Health Clinic	Hokkaido, Sapporo		Japan	001-0010
54	Arai Clinic	Hyogo, Amagasaki		Japan	660-0882
55	Tatsuta Clinic	Hyogo, Kobe		Japan	651-0097
56	Kishiro Mental Clinic	Kanagawa, Kawasaki		Japan	214-0014
57	Yuge Neuropsychiatric Hospital	Kumamoto, Kumamoto		Japan	861-8002
58	Arata Clinic	Nagasaki, Nagasaki		Japan	852-8154
59	Nara Medical University Hospital	Nara, Kashihara		Japan	634-8522
60	Rainbow and Sea Hospital	Saga, Karatsu		Japan	847-0031
61	National Center of Neurology and Psychiatry	Tokyo, Kodaira		Japan	187-8851
62	Sancha Mental Clinic	Tokyo, Setagaya-ku		Japan	154-0004
63	Maynds Tower Mental Clinic	Tokyo, Shibuya-ku		Japan	151-0053
64	Ichigaya Himorogi Clinic	Tokyo, Shinjuku-ku		Japan	162-0843
65	Specialist Psychiatric Healthcare Centre in Lodz	Lodz		Poland	91-229
66	Federal State Budget Institution "Mental Health Research Center"	Moscow		Russian Federation	115522
67	SBI of HC "Z. P. Solovyov Scientific&pract psychoneurolog.Cent"	Moscow		Russian Federation	129110
68	SHI "Reg.Clin.Psychiatric Hosp.of Saint Sophia"	Saratov		Russian Federation	410060
69	FSBEI of HE Smolensk State Medical University	Smolensk		Russian Federation	214019
70	SBHI "Psychiatric Hospital #1 P.P.Kashchenko"	St. Petersburg		Russian Federation	190121
71	FSBI Bekhterev Net.Med.Res.Cen.of Psych&Neuro	St. Petersburg		Russian Federation	192019
72	LLC "MK-Med"	St. Petersburg		Russian Federation	197373
73	MUDr. Beata Dupejová	Banska Bystrica		Slovakia	974 04
74	J & J SMART, s.r.o., psychiatric clinic	Bratislava		Slovakia	81107
75	MENTUM s.r.o.	Bratislava		Slovakia	82007
76	EPAMED s.r.o.	Kosice		Slovakia	040 01
77	CENTRUM ZDRAVIA R.B.K, s.r.o., psychiatric clinic	Svidnik		Slovakia	089 01
78	Crystal Comfort s.r.o	Vranov nad Toplou		Slovakia	093 01
79	Hospital Universitario Fundación Alcorcón	Alcorcón		Spain	28922
80	Hospital Clínic de Barcelona	Barcelona		Spain	08036
81	Hospital Ramón y Cajal	Madrid		Spain	28034
82	Hospital Puerta de Hierro	Majadahonda		Spain	28222
83	Centro de Salud de San Juan	Salamanca		Spain	37005
84	Hospital Universitario Marqués de Valdecilla	Santander		Spain	39008

Sponsors and Collaborators

• Boehringer Ingelheim

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT04521478
• Other Study ID Numbers: 1402-0011; 2019-004264-21
• First Posted: Aug 20, 2020
• Last Update Posted: Aug 23, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major; Quetiapine Fumarate

Study Results

No Results Posted as of Aug 23, 2022