* to evaluate the safety and tolerability of Lu AF90103 following single ascending intravenous (i.v.) doses* to investigate the pharmacokinetics (PK) of Lu AF90103 (prodrug) and Lu AF88361 (drug) in plasma and cerebrospinal fluid (CSF) following…
ID
Source
Brief title
Condition
- Mood disorders and disturbances NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Main Endpoints
Safety
* adverse events
* absolute values and changes from baseline in clinical safety laboratory test
values (incl. urine kidney biomarkers), vital signs, weight, and ECG parameter
values
* potentially clinically significant clinical safety laboratory test values
(incl. urine kidney biomarkers), vital signs, weight changes, and ECG parameter
values
* changes from baseline in the Psychotomimetic States Inventory (PSI) and the
Clinically Administered Dissociative States Scale (CADSS), used to assess
psychotomimetic side effects.
Pharmacokinetics
* area under the concentration-time curve from zero to infinity in plasma and
CSF (AUC0-inf) for Lu AF90103 and Lu AF88361, defined as AUC0-t + Clast × t* /
ln2 (where Clast is the last quantifiable concentration and t* is the apparent
elimination half-life)
* Concentration at time zero (C0) following infusion of Lu AF90103 in plasma,
* maximum observed concentration (Cmax) in plasma and CSF for Lu AF88361 and in
CSF for Lu AF90103
* total clearance, defined as dose / AUC0-inf (plasma) (CL)
* apparent elimination half-life in plasma and CSF for Lu AF90103 and Lu
AF88361 (t*)
* nominal time corresponding to the occurrence of Cmax for Lu AF90103 in CSF
and Lu AF88361 in plasma and CSF (tmax)
* apparent volume of distribution, defined as CL × t* / ln2 (Vz)
* Plot of a cumulative excretion and amount remaining to be excreted for Lu
AF90103 and Lu AF88361 will made based on urine data.
* Metabolic ratio (MR), defined as AUCmetabolite/AUC parent
Pharmacodynamics -EEG
* Changes to time matched baseline in AUC of medial prefrontal (FZ and CZ
electrodes) high gamma (100-170 HZ) in the resting state
Secondary outcome
Not applicable
Background summary
The planned first-in-human study is an interventional, randomized,
double-blind, placebo-controlled, single-ascending dose study investigating the
safety, tolerability, and PK and PD properties of Lu AF90103 in healthy men.
The aim is to develop an IV antidepressant that addresses depressive symptoms
with fast and sustained efficacy that provides significant and clinically
meaningful effect within 2 days of first administration, maintained effect
after repeated treatment, and acceptable safety and tolerability compared to
standard of care.
Study objective
* to evaluate the safety and tolerability of Lu AF90103 following single
ascending intravenous (i.v.) doses
* to investigate the pharmacokinetics (PK) of Lu AF90103 (prodrug) and Lu
AF88361 (drug) in plasma and cerebrospinal fluid (CSF) following administration
of single ascending i.v. doses
* estimation of fraction of Lu AF90103 and Lu AF88361 eliminated in urine
* to investigate the pharmacodynamic (PD) effects of Lu AF90103 in healthy men
by examining resting state quantitative electroencephalography (qEEG)
parameters
Study design
This is an interventional study consisting of two parts. Part A is a
randomized, double-blind, placebo-controlled, single-ascending dose study
investigating the safety, tolerability, and pharmacokinetic and -dynamic
properties of Lu AF90103 and Part B is a randomized, doubleblind,
cross-over study to investigate the safety profile after administration of Lu
AF90103 as an infusion over 15 min and 45 min to healthy men.
Intervention
The IMPs in this study are:
Lu AF90103 - 50 mg, powder for solution for infusion, intravenous
Placebo * powder for solution for infusion, intravenous
Study burden and risks
Since the study is being executed in healthy volunteers, there are no
anticipated benefits of the IMP. Please see the IB for further information.
Ottiliavej 9
Valby 2500
DK
Ottiliavej 9
Valby 2500
DK
Listed location countries
Age
Inclusion criteria
1. The subject is able to read and understand the Informed Consent Form.
2. The subject has signed the study-specific Informed Consent Form.
3. The subject is a man
4. The subject is *18 and *45 years of age at the Screening Visit for Cohorts
A1 to A6 (excluding cohort A2b) or *55 to *65 for subjects in the CSF sampling
Cohorts A2b and A7.
5. The subject has a BMI *18.5 and *30 kg/m2, body weight *60kg, at the
Screening Visit and at the Baseline Visit.
Exclusion criteria
1. The subject has taken disallowed medication <1 week prior to the first dose
of IMP or <5 half-lives prior to the Screening Visit for any medication taken.
Disallowed medication is any prescribed medication or over-the-counter
medication as well as any herbal medicine known to interfere with the metabolic
CYP pathways, such as St. John*s Wort, ginseng, milk thistle, and echinacea.
Subjects who have taken any non-prescribed systemic or topical medication may
participate in the study if, in the opinion of the investigator, the medication
will not interfere with the study procedures, study results, or compromise
safety.
2. The subject has orthostatic hypotension, defined as a decrease in systolic
blood pressure *20 mmHg from supine to standing within 3 minutes, at the
Screening Visit or at the Baseline Visit.
3. The subject has a QTc interval >430 ms (Fridericia*s correction) at the
Screening Visit, as calculated by the ECG equipment and evaluated by the
investigator. The ECG may be repeated if any of the values are out of range or
abnormal.
4. The subject has or has had any clinically significant immunological,
cardiovascular, respiratory, metabolic, renal, hepatic, gastrointestinal,
endocrinological, haematological, dermatological, venereal, neurological, or
psychiatric disease or other major disorder.
5. The subject has a family history of psychosis in a first degree relative
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2019-004271-39-NL |
| CCMO | NL77259.056.21 |