Efficacy and Safety of AP707 in Patients with Borderline Personality Disorder: A Phase II, Randomized, Double-Blind, Placebo-Controlled Trial
- Trial ID
- 2024-510873-11-00
- Protocol
- Illuminate
- Sponsor
- Apurano Pharmaceuticals GmbH
Trial statistics
Diseases & Conditions
Objectives
The primary objective is to evaluate the efficacy of AP707 in patients with borderline personality disorder compared to placebo using the Zanarini Rating Scale for Borderline Personality Disorder and the Borderline Symptom Scale. 5, 4, 9
Secondary objectives include the assessment of efficacy regarding:
- Clinical Global Impression Severity Scale and Patient Global Impression of Change;
- State-Trait Anger Expression Inventory 2 and Difficulties in Emotion Regulation Scale;
- Depression, anxiety, and impulsivity;
- Specific domains of the Zanarini Rating Scale, including interpersonal, cognitive, and affective sector scores;
- NRS-Pain score and rescue medication intake.
Participants
The sponsor did not provide information regarding the total number of participants. The study population consists of male and female patients diagnosed with borderline personality disorder according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria. Participants must be 18 years of age or older at the time of informed consent. Inclusion requires confirmation of the diagnosis through a structured interview for DSM-5 Personality Disorder (SCID-5-PD). Eligible individuals must have a score of ≥ 10 on the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) at screening. Participants are required to maintain a stable dosage of psychiatric medication, such as antidepressants, mood stabilizers, or antipsychotics, for at least 28 days prior to screening, or they must be not taking any such medication. Additional requirements include the use of effective contraception, proficiency in the German language, and possession of a smartphone for electronic data capture application installation.
Plans and Procedures
This phase II, double-blind, placebo-controlled clinical trial is designed to evaluate the efficacy and safety of AP707, an oromucosal spray containing adezunap, in the treatment of borderline personality disorder. The study methodology involves comparing the test product against a placebo to determine improvements in clinical symptoms. The primary endpoints are measured using the Zanarini Rating Scale for Borderline Personality Disorder and the Borderline Symptom Scale. The research process begins with a screening visit to confirm eligibility via the Structured Clinical Interview for DSM-5 Personality Disorder and assessment of baseline symptom severity. Following screening, participants undergo treatment and subsequent follow-up assessments to monitor clinical changes and safety. The trial includes various secondary endpoints, such as evaluations of anger, impulsivity, and depressive symptoms. The total duration of participant involvement extends through the end-of-study visit, which includes assessments up to 18 weeks of follow-up.
Treatment
The experimental medication, AP707, consists of the active substance adezunap. It is administered in the form of an oromucosal spray suspension at a dosage of 16.5 mg via the oromucosal route.
The control group receives a placebo as a non-experimental treatment in this double-blinded, placebo-controlled study for the management of borderline personality disorder.
Efficacy
The efficacy of AP707 in the treatment of borderline personality disorder is assessed through several primary and secondary endpoints. The primary efficacy evaluation is based on the baseline adjusted difference in the mean change from baseline in total scores for the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) and the Borderline Symptom Scale (BSL-23) at the end-of-treatment (EoT).
Secondary efficacy assessments conducted at EoT include:
- The proportion of responders and the time to first response for both ZAN-BPD and BSL-23, categorized by a 30% or 50% reduction in total scores.
- The baseline adjusted difference in the mean change from baseline in the Clinical Global Impression-Severity (CGI-S) score, measured at EoT and throughout multiple visits.
- The proportion of participants per Clinical Global Impression-Improvement (PGI-C) score at EoT.
- Changes in anger-related metrics using the State-Trait Anger Expression Inventory-2 (STAXI-2), including Trait-Anger, Anger Expression-Out, Anger Expression-In, and Anger Control.
- The baseline adjusted difference in the mean change from baseline in the Difficulties in Emotion Regulation Scale (DERS-36) total score.
- Changes in depressive symptoms using the Patient Health Questionnaire (PHQ-9) and the Montgomery-Åsberg Depression Rating Scale (MADRS).
- Changes in anxiety levels using the State-Trait Anxiety Inventory (STAI) for both State-Anxiety and Trait-Anxiety.
- Changes in impulsivity measured by the Barratt Impulsiveness Scale 15 (BIS-15) and specific ZAN-BPD sector scores, including impulsive, interpersonal, cognitive, and affective sectors.
- Changes in the Numerical Rating Scale for Pain (NRS-Pain) score.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Signed and dated study informed consent forms, demonstrating willingness to comply with trial instructions;
- Zanarini rating scale for borderline personality disorder (ZAN-BPD, 0-36) of ≥ 10 at screening;
- Female and male participants aged 18 years or older at the time of informed consent signa-ture;
- Participants with main diagnosis of borderline personality disorder (BPD) per Diagnostic and Statistical Manual of Mental Disorders (DSM-5);
- BPD was confirmed by structured interview for DSM-5 Personality Disorder (SCID-5-PD) at screening visit;
- Stable dosage of psychiatric medication (e.g., antidepressants, mood stabilizers, antipsychotics) for at least 28 days prior to screening or no medication intake. This does not apply to pro re nata medication;
- Participants commitment to use effective contraception methods (<1% failure rate) from screening to end of follow-up. This does not apply for persons of abstinence from sexual inter-course or non-childbearing potential (i.e. post-menopausal, surgically sterile). An effective contraception usually includes the use of a barrier method with another contraception method simultaneously;
- Good command of German language, to fully understand the questionnaires;
- Participants must have a smartphone on which the EDC application can be installed;
Exclusion Criteria
- Medical history of hypersensitivity or intolerance to the IMP or its ingredients or to ingredients of similar chemical structure;
- Known intolerance to cannabinoids or cannabis products;
- Known use of cannabis products within the last 28 days before screening or during the study;
- Females who are currently pregnant or lactating or intend to become pregnant during the trial;
- Participation in another clinical trial within the last four weeks prior to screening or the administration of another IMP within 5 half-lives before screening;
- Participant is considered to belong to a vulnerable population (e.g. not capable of giving consent independently, imprisoned, other);
- Known severe cardiovascular disease such as cardiac insufficiency (New York Heart Association Classification (NYHA) Class III-IV), acute myocardial infarction, any form of cardiomyopathy (not to be counted as exclusion criteria: hypertension, adjusted cardiac arrhythmias, recovered from infectious heart diseases);
- Known liver disease or alanine aminotransferase (ALT, GPT) or aspartate aminotransferase (AST, GOT) or alkaline phosphatase (AP, ALP) level ≥ 2.5 x upper limit of normal (ULN) or bilirubin ≥ 1.5 x ULN at screening;
- Known kidney disease or serum creatinine ≥ 1.5 x ULN or estimated glomerular filtration rate < 60 mL/min at screening;
- Acute suicidality according to clinical judgement (based on psychopathological findings and C-SSRS interview);
- Initiation or change in any type or frequency of psychotherapy within 3 months prior to screening. Exceptions: a) Participants with ongoing, stable outpatient psychotherapy > 3 months prior to screening (and intend to maintain the same frequency during the trial) could qualify as per clinical judgement of the investigator. b) Participants who completed inpatient therapy at least 14 days prior to the screening visit could qualify as per clinical judgement of the investigator.
- Clinical diagnosis of paranoid, schizoid, schizotypal and acute severe substance use disorder according to DSM-5;
- Lifetime diagnosis for schizophrenia spectrum and other psychotic disorders, schizoaffective disorder, schizophreniform disorder, bipolar disorder, or delusional disorder as confirmed by the SCID-5-PD interview at the screening visit;
- The intake of at least one of the following medications before and during the study: Clozapine, Carbamazepine, Valproic acid, St. John’s wort, grapefruit juice, constant benzodiazepine use. Exception: The therapy had been discontinued at least 21 days prior to screening and the discontinuation must have been independent of participation in the study;
- Any psychiatric condition that, in the investigator's opinion, would prevent the participant from adhering to the protocol or completing the clinical trial per protocol;
- Any clinically significant finding of the physical examination that would jeopardize the participant´s safety during the trial;
- Participant is study investigator or personnel of a trial site, the sponsor or involved service providers and/or their immediate families (partner, spouse, parent, child, or sibling, whether biological or legally adopted);
- An ECG QTc limit value of more than 450 milliseconds in men and an ECG QTc limit value of more than 470 milliseconds in women.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Germany | Not Yet Recruiting | 01 May 2026 | 154 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
AP707 | Test | OROMUCOSAL SPRAY, SUSPENSION | OROMUCOSAL | 16.5 | 17 | PRD10071357 |
Placebo | Placebo | N/A | — | — | — | N/A |