Clinical Trials Register

Summary
EudraCT Number:	2019-004255-36
Sponsor's Protocol Code Number:	Cesar
National Competent Authority:	Sweden - MPA
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2020-06-01
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Sweden - MPA

A.2

EudraCT number

2019-004255-36

A.3

Full title of the trial

Cesar - an open, randomized controlled phase II study, comparing Naltrexon and Fluoxetin treating Compulsive Sexual Behavior Disorder.

Cesar - en öppen randomiserad kontrollerad fas II-studie som jämför Naltrexon med Fluoxetin vid behandling av tvångsmässig sexuell beteendestörning.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Cesar - an open, randomized controlled phase II study, comparing Naltrexon and Fluoxetin treating Compulsive Sexual Behavior Disorder.

Cesar - en öppen randomiserad kontrollerad fas II-studie som jämför Naltrexon med Fluoxetin vid behandling av tvångsmässig sexuell beteendestörning.

A.3.2

Name or abbreviated title of the trial where available

Cesar-studien

A.4.1

Sponsor's protocol code number

Cesar

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Karolinska Universitetssjukhuset
B.1.3.4	Country	Sweden
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	SLSO
B.4.2	Country	Sweden
B.4.1	Name of organisation providing support	Region Västerbotten
B.4.2	Country	Sweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Karolinska Universitetssjukhuset
B.5.2	Functional name of contact point	Centrum för psykitariforskning
B.5.3	Address:
B.5.3.1	Street Address	Norra Stationsgatan 69
B.5.3.2	Town/ city	Stockholm
B.5.3.3	Post code	113 64
B.5.3.4	Country	Sweden
B.5.6	E-mail	josephine.savard@sll.se

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Naltrexon Vitaflo 50 mg, tablets for oral treatment.
D.2.1.1.2	Name of the Marketing Authorisation holder	AOP Orphan Pharmaceuticals AG
D.2.1.2	Country which granted the Marketing Authorisation	Sweden
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	NALTREXONE
D.3.9.1	CAS number	16590-41-3
D.3.9.4	EV Substance Code	SUB09143MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Fluoxetine Orion
D.2.1.1.2	Name of the Marketing Authorisation holder	Orion Corporation
D.2.1.2	Country which granted the Marketing Authorisation	Sweden
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Fluoxetine Orion
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	FLUOXETINE HYDROCHLORIDE
D.3.9.1	CAS number	59333-67-4
D.3.9.4	EV Substance Code	SUB02226MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	20 to 40
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule, hard
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Compulsive Sexual Behavior Disorder

Tvångsmässig sexualitet/sexuell störning.

E.1.1.1

Medical condition in easily understood language

Compulsive Sexual Behavior Disorder

Tvångsmässig sexualitet/sexuell störning.

E.1.1.2

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Is treatment with naltrexone more efficient than Fluoxetine in patients with Compulsive Sexual Behavior Disorder.

Är behandling med Naltrexon mer effektivt än Fluoxetin vid tvångsmässig sexuell beteendestörning?

E.2.2

Secondary objectives of the trial

- If treatment with naltrexone is more efficient than fluoxetin in patients with Compulsive Sexual Behaviour Disorder, which clinical, psychosocial or biological factors can predict treatment respons?
- Is there any difference in drop out and treatment compliance between the two treatment groups?
- Which side effects of the study drug and the standard treatment is reported in this patient group?
- Is there any connection between drop out and reports of side effects and/or effect?
- Is it any difference if the patient whish to resume the treatment?
- In what way does compulsive sexual behavoiur disorder correlate with impulsiveness, expeience of violence/trauma and suicidality?
- Is there any biological markers associated with compulsive sexual behaviour disorder and clinical parameters in the patient group?

• Om Naltrexon är mer effektivt än Fluoxetin för att behandla tvångsmässig sexualitet, vilka kliniska, psykosociala eller biologiska faktorer kan vara en prediktor för respons? (Vilka faktorer kan förutse behandlingsrespons?)
• Är det någon skillnad i avhopp drop out och följsamhet mellan grupperna?
• Vilka biverkningar rapporteras av preparaten i den här patientgruppen?
• Finns det någon koppling mellan drop out och biverkningsrapportering och/eller effekt?
• Är det någon skillnad på frågan om man önskar återuppta läkemedelsbehandlingen? (v 14)
• Hur korrelerar tvångsmässig sexualitet med kliniska faktorer så som bland annat impulsivitet, erfarenhet av våld/trauma och suicidalitet?
• Finns biologiska markörer som är associerade med tvångsmässig sexualitet och kliniska parametrar i den gruppen?

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Age 18 - 65 years
- Signed Informed Consent
- Able to understand Swedish language, written and spoken. Be able to use internet.
- Willingness to attend all visits including blood sampling and urine analysis
- Fulfill the criterias of Compulsive Sexual Behaviour Disorder
- Women of childbearing potential must practice a highly effective method of birth control throughout the study

• Fyllda 18–65 års ålder (fyller ej 66 under studieperioden)
• Undertecknat informerat samtycke
• Kunna förstå det svenska språket muntligt och skriftligt, skriva på svenska och kunna använda internet/ha tillgång till dator.
• Är villig att delta i alla besök inklusive att lämna blod och urinprover.
• Uppfylla kriterier för tvångsmässig sexualitet utifrån förslagna diagnoskriterier ICD-11 (v.g. se Bilaga 19.2) och kriterierna enligt ursprungsförslaget till DSM V (Bilaga 19.2).
• För fertila kvinnor: användande av effektivt preventivmedel under hela studieperioden. Som effektivt preventivmedel räknas något av följande:
o Kombinerade hormonella preventivmedel (östrogen och gestagen) som hämmar ägglossningen: orala, intravaginala eller transdermala
o Progesteron-hormonella preventivmedel som hämmar ägglossning: orala, injicerbara eller implanterbara
o Spiral (hormon- eller kopparspiral)
o Bilateral äggledarocklusion
o Vasektomerad partner
o Sexuell avhållsamhet, att avstå från heterosexuella vaginala samlag under hela studien.

E.4

Principal exclusion criteria

- AST and ALT greater than 3 x ULN
- Ongoing treatment with opioids or benzodiazepines
- Self reported use of illegal drugs during the last month, or presence of abuse in urine at inclusion
- Hazardous consumption of alcohol during the last month, or alcohol abuse. AUDIT >8.
- Severe psychiatric desease e.g. psychosis or major depression with immediate need of helath care
- History of hepatic- or renal impairment.
- Severe somatic condition including unstable heart disease or uncontrolled seizures.
- Current treatment with SSRI or Naltrexone, or history of allergy to these treatments
- Changes in treatment regimen or doses the last three month of following therapies: anti depressive, ADHD (minor changes weekdays but not weekends may be accepted, as judged by the investigator) antimanic agents, anti psychotic, cortisone, testosterone, L-Dopa
- Current use of medications which have serious interactions with fluoxetine e.g. MAO-inhibitors, cocillana-etylmorfin and metoprolol.
- Pregnancy, lactating or inadequate birth control within women of childbearing potential.
- Current psychotherapy. Family counselling may be accepted, as judged by the study psychologist.
- Any psychological condition that may interfere the patients health or the scientific parts of the study, e.g. intelectual disability
- Already enrolled into a clinical trial

• Förhöjda levervärden (mer än tre gånger det övre referensområdet för ALAT, ASAT).
• Behandling med opioder eller bensodiazepiner.
• Olaglig självrapporterad användning av droger under den senaste månaden eller laboratorieverifierat positivt urinprov för droger.
• Riskbruk av alkohol sista månaden (>14 glas/v för män, > 9 kvinnor) eller alkoholberoende. AUDIT > 8 kommer särskilt beaktas.
• Allvarlig psykisk störning som aktuell psykos eller svår depression som kräver omedelbar handläggning/behandling.
• Historia av lever- eller njursvikt.
• Allvarlig somatisk sjukdom inklusive instabil hjärtsjukdom eller okontrollerad krampsjukdom.
• Pågående behandling med SSRI eller Naltrexon, eller tidigare allergisk reaktion mot dessa preparat.
• Förändring av medicinering eller dosering under de senaste 3 månaderna inräknat antidepressiva, ADHD-medicinering, stämningsstabiliserare, antipsykotika, kortison, testosteron eller prekursor av dopamin, såsom L-Dopa. Mindre justeringar så som ADHD-medicin på vardagar men inte helgtid, accepteras om det inte är en större dosförändring (bedöms av psykiater) och pågått under minst 3 månader.
• Medicinering som inte är kompatibel med Naltrexon eller Fluoxetin enl FASS t.ex. Mao-hämmare, cocillana-etylmorfin, metoprolol.
• Graviditet, amning eller inadekvat preventivmedel hos fertila kvinnor
• Pågående psykoterapeutisk behandling. Stödgrupper och familjerådgivning (om inte direkt kopplat till den sexuella problematiken kan accepteras, bedöms av studiepsykolog).
• Psykologiskt tillstånd som kan äventyra patientens hälsa eller de vetenskapliga delarna av studien, detta bedöms av läkare och psykolog (exempelvis intellektuell funktionsnedsättning).
• Deltagande i annan studie utanför ANOVA.

E.5 End points

E.5.1

Primary end point(s)

Questionnaire HD: CAS

Självskattningsskalan: HD: CAS

E.5.1.1

Timepoint(s) of evaluation of this end point

Measured at week 2, week 4, week 6, week 8 and at Follow Up, six weeks after end of treatment.

Mäts i vecka 2, vecka 4, vecka 6 och vecka 8 samt vid Follow up sex veckor efter behandlingsslut.

E.5.2

Secondary end point(s)

- Sub analysis of clinical characteristics e.g. psychiatric co-morbidity, questionnaires and biological markers. Measured at baseline, week 8, week 14 and future analysis
- Number of drop outs, reported compliance, pill count, verified intake (measured by urine and blood analysis at week 8 and week 14) between the two groups.
- Differences in reported side effects and comparison with the above variables. Measured at week 8.
- Answer in the web-platform, on the direct question of resuming the treatment. Measured at week week 14
- Analysis of screening and measurements of KIVS, CTQ and MINI at baseline.
- Analysis of biological material at baseline and future analysis.

• Subanalyser utifrån klinisk karaktäristika så som psykiatrisk samsjuklighet, svar på skattningsformulär och biologiska markörer. Mäts vid baseline, v 8, v 14 och framtida biologiska analyser
• Antalet avhopp (drop out), rapporterad följsamhet, pill count (drug accountability), verifierat intag (urin/blodprov) mellan grupperna. Mäts vid v 8 och v 14.
• Skillnad i biverkningsrapportering och jämförelse med variablerna ovan. Mäts v 8.
• Svar på direkt fråga i web-plattform om önskemål om att återuppta behandlingen. Mäts v 14.
• Analyser utifrån svar på screening- och mätbatterier KIVS, CTQ, MINI, vid baseline
• Analyser på biologiskt material, baseline och efter studiens avslutande (framtida analyser)

E.5.2.1

Timepoint(s) of evaluation of this end point

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

After completion of the study the subjects will be asked to sign in as patients at ANOVA. If the subject would like to resume the treatment it will be discussed with .............

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-06-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-10-05

P. End of Trial
P.	End of Trial Status	Ongoing

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