CTH120 First-in-Human Study: Single and Multiple Ascending Doses and Potential Food Interaction
NCT Number: NCT06480968
Acronym: FIH-CTH120
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: Fragile X Syndrome
Interventions: DRUG: CTH120|OTHER: Placebo
Sponsor: Connecta Therapeutics, S.L.
Collaborators: Adknoma Health Research|Hospital del Mar Research Institute|Ministerio de Ciencia e Innovación, Spain
Sex: ALL
Age: ADULT
Enrollment: 68
Study Design: Allocation: RANDOMIZED|Intervention Model: SEQUENTIAL|Masking: QUADRUPLE (PARTICIPANT, CARE_PROVIDER, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2023-06-23
Completion Date: 2025-03
Locations: Hospital del Mar Medical Research Institute (IMIM), Barcelona, 08003, Spain

Summary:
The purpose of this First-in-Human Phase I study is to investigate the safety, tolerability and pharmacokinetics of CTH120 in adult healthy volunteers.

Primary Outcome Measures: Treatment-emergent adverse events (TEAEs)., Primary Safety and Tolerability endpoint for FIH-CTH120-SAD and FIH-CTH120-MAD (Not applicable for FIH-CTH120-FI).

• AEs will be described in terms of result, frequency, intensity, medical decision, relation with study drug, as well as treatment received and subject retirement, duration, and time elapsed. AEs will also be listed and coded using the MedDRA Dictionary (version 26.0) for the term's codification., From Day 1 to End-of-study: EOS will be on Day 8 (± 1 day) for FIH-CTH120-SAD and on Day 15 (+ 2 days) for FIH-CTH120-MAD|Treatment-emergent potentially clinically significant abnormalities (PSCAs) in blood pressure (mmHg), Primary Safety and Tolerability endpoint for FIH-CTH120-SAD and FIH-CTH120-MAD (Not applicable for FIH-CTH120-FI).

• Blood pressure (mmHg) will be measured in the supine position following a 5 min rest., From Day 1 to End-of-study (EOS): on Day 8 (± 1 day) for FIH-CTH120-SAD, and on Day 15 (+ 2 days) for FIH-CTH120-MAD|Treatment-emergent potentially clinically significant abnormalities (PSCAs) in pulse rate (bpm), Primary Safety and Tolerability endpoint for FIH-CTH120-SAD and FIH-CTH120-MAD (Not applicable for FIH-CTH120-FI).

• Pulse rate (bpm) will be measured in the supine position following a 5 min rest., From Day 1 to End-of-study (EOS): on Day 8 (± 1 day) for FIH-CTH120-SAD, and on Day 15 (+ 2 days) for FIH-CTH120-MAD|Treatment-emergent potentially clinically significant abnormalities (PSCAs) in oral body temperature (ºC), Primary Safety and Tolerability endpoint for FIH-CTH120-SAD and FIH-CTH120-MAD (Not applicable for FIH-CTH120-FI).

• Oral body temperature (ºC) will be measured using an automated vital sign monitor device., From Day 1 to End-of-study (EOS): on Day 8 (± 1 day) for FIH-CTH120-SAD, and on Day 15 (+ 2 days) for FIH-CTH120-MAD|Treatment-emergent potentially clinically significant abnormalities (PSCAs) in electrocardiogram (ECG) values: normal sinus rhythm (NSR), Primary Safety and Tolerability endpoints for FIH-CTH120-SAD and FIH-CTH120-MAD (Not applicable for FIH-CTH120-FI)

• Computerized 12-lead electrocardiogram (ECG) recordings will be obtained. Each lead shall be recorded for at least 3 beats at a speed of 25 mm/s. Triplicate recordings will be made at the time points evaluated. The following parameter will be recorded: normal sinus rhythm (NSR)., From Day 1 to End-of-study (EOS): on Day 8 (± 1 day) for FIH-CTH120-SAD, and on Day 15 (+ 2 days) for FIH-CTH120-MAD|Treatment-emergent potentially clinically significant abnormalities (PSCAs) in electrocardiogram (ECG) values: heart rate (bpm), Primary Safety and Tolerability endpoints for FIH-CTH120-SAD and FIH-CTH120-MAD (Not applicable for FIH-CTH120-FI)

• Computerized 12-lead electrocardiogram (ECG) recordings will be obtained. Each lead shall be recorded for at least 3 beats at a speed of 25 mm/s. Triplicate recordings will be made at the time points evaluated. The following parameter will be recorded: heart rate (bpm)., From Day 1 to End-of-study (EOS): on Day 8 (± 1 day) for FIH-CTH120-SAD, and on Day 15 (+ 2 days) for FIH-CTH120-MAD|Treatment-emergent potentially clinically significant abnormalities (PSCAs) in electrocardiogram (ECG) values: PR interval (ms), Primary Safety and Tolerability endpoints for FIH-CTH120-SAD and FIH-CTH120-MAD (Not applicable for FIH-CTH120-FI)

• Computerized 12-lead electrocardiogram (ECG) recordings will be obtained. Each lead shall be recorded for at least 3 beats at a speed of 25 mm/s. Triplicate recordings will be made at the time points evaluated. The following parameter will be recorded: PR interval (ms)., From Day 1 to End-of-study (EOS): on Day 8 (± 1 day) for FIH-CTH120-SAD, and on Day 15 (+ 2 days) for FIH-CTH120-MAD|Treatment-emergent potentially clinically significant abnormalities (PSCAs) in electrocardiogram (ECG) values: QRS duration (ms), Primary Safety and Tolerability endpoints for FIH-CTH120-SAD and FIH-CTH120-MAD (Not applicable for FIH-CTH120-FI)

• Computerized 12-lead electrocardiogram (ECG) recordings will be obtained. Each lead shall be recorded for at least 3 beats at a speed of 25 mm/s.Triplicate recordings will be made at the time points evaluated. The following parameter will be recorded: QRS duration (ms)., From Day 1 to End-of-study (EOS): on Day 8 (± 1 day) for FIH-CTH120-SAD, and on Day 15 (+ 2 days) for FIH-CTH120-MAD|Treatment-emergent potentially clinically significant abnormalities (PSCAs) in electrocardiogram (ECG) values: QT (ms), Primary Safety and Tolerability endpoints for FIH-CTH120-SAD and FIH-CTH120-MAD (Not applicable for FIH-CTH120-FI)

• Computerized 12-lead electrocardiogram (ECG) recordings will be obtained. Each lead shall be recorded for at least 3 beats at a speed of 25 mm/s.Triplicate recordings will be made at the time points evaluated. The following parameter will be recorded: QT (ms)., From Day 1 to End-of-study (EOS): on Day 8 (± 1 day) for FIH-CTH120-SAD, and on Day 15 (+ 2 days) for FIH-CTH120-MAD|Treatment-emergent potentially clinically significant abnormalities (PSCAs) in electrocardiogram (ECG) values: QTcF (ms), Primary Safety and Tolerability endpoints for FIH-CTH120-SAD and FIH-CTH120-MAD (Not applicable for FIH-CTH120-FI)

• Computerized 12-lead electrocardiogram (ECG) recordings will be obtained. Each lead shall be recorded for at least 3 beats at a speed of 25 mm/s.Triplicate recordings will be made at the time points evaluated. The following parameter will be recorded: QTcF (ms)., From Day 1 to End-of-study (EOS): on Day 8 (± 1 day) for FIH-CTH120-SAD, and on Day 15 (+ 2 days) for FIH-CTH120-MAD|Treatment-emergent potentially clinically significant abnormalities (PSCAs) in safety laboratory parameters: haematology, Primary Safety and Tolerability endpoints for FIH-CTH120-SAD and FIH-CTH120-MAD (Not applicable for FIH-CTH120-FI). The following tests will be performed:

• Haematology: complete blood count (complete blood count \[CBC\]; including haemoglobin, haematocrit, red blood cell \[RBC\], white blood cell (WBC), platelet count, and percent and absolute differential count (neutrophils, lymphocytes, eosinophils, monocytes, basophils, and other cells)., From Day 1 to End-of-study (EOS): on Day 8 (± 1 day) for FIH-CTH120-SAD, and on Day 15 (+ 2 days) for FIH-CTH120-MAD|Treatment-emergent potentially clinically significant abnormalities (PSCAs) in safety laboratory parameters: serum chemistry, Primary Safety and Tolerability endpoints for FIH-CTH120-SAD and FIH-CTH120-MAD (Not applicable for FIH-CTH120-FI). The following tests will be performed:

• Serum chemistry: sodium, potassium, chloride, non-fasting glucose, urea, creatinine, calcium, phosphate, magnesium, total and direct bilirubin, total protein, albumin, ALT, AST, ALP, lactate dehydrogenase., From Day 1 to End-of-study (EOS): on Day 8 (± 1 day) for FIH-CTH120-SAD, and on Day 15 (+ 2 days) for FIH-CTH120-MAD|Treatment-emergent potentially clinically significant abnormalities (PSCAs) in safety laboratory parameters: coagulation, Primary Safety and Tolerability endpoints for FIH-CTH120-SAD and FIH-CTH120-MAD (Not applicable for FIH-CTH120-FI). The following tests will be performed:

• Coagulation parameters: activated partial thromboplastin time (aPTT), PT and INR., From Day 1 to End-of-study (EOS): on Day 8 (± 1 day) for FIH-CTH120-SAD, and on Day 15 (+ 2 days) for FIH-CTH120-MAD|Treatment-emergent potentially clinically significant abnormalities (PSCAs) in safety laboratory parameters: urinalysis, Primary Safety and Tolerability endpoints for FIH-CTH120-SAD and FIH-CTH120-MAD (Not applicable for FIH-CTH120-FI). The following tests will be performed:

• Urinalysis parameters:

* Macroscopic examination: specific gravity, pH, protein, glucose, ketones, blood, bilirubin, leukocyte, urobilinogen, and nitrite.
* Microscopic examination: RBCs, WBCs, epithelial cells, casts, crystals, bacteria, and yeast., From Day 1 to End-of-study (EOS): on Day 8 (± 1 day) for FIH-CTH120-SAD, and on Day 15 (+ 2 days) for FIH-CTH120-MAD|Psychometric tests: Hospital Anxiety/Depression rating Scale (HADS), Primary Safety and Tolerability endpoints for FIH-CTH120-SAD and FIH-CTH120-MAD (Not applicable for FIH-CTH120-FI).

• HADS: Self-reported questionnaire used to detect depression and anxiety. It consists of 14 items (7 related to depression and 7 to anxiety) scored using a 4-point Likert scale (each item ranging from 0 to 3). Two scores are generated one for depression and one for anxiety each score ranging from 0 to 21. Higher scores indicate greater levels of anxiety or depression. Both scores can be categorized into: Normality (0-7); Probable case of anxiety or depression (8-10); Case of anxiety or depression (11-21)., FIH-CTH120-SAD: on Day -1 and Day 2; FIH-CTH120-MAD: on Day -1, Day 1, and Day 7|Psychometric tests:Immediate Mood Scaler (IMS)., Primary Safety and Tolerability endpoints for FIH-CTH120-SAD and FIH-CTH120-MAD (Not applicable for FIH-CTH120-FI).

• IMS: The IMS is a tool to remotely and quickly track mood changes related to depression and anxiety in the moment. It consists of 22 items, scored between 1 and 7. The total score for this scale is the sum of the scores on all 22 items: ranging from 22 to 154. Lower scores reflect more negative mood states., FIH-CTH120-SAD: on Day -1 and Day 2; FIH-CTH120-MAD: on Day -1, Day 1, and Day 7|Area under the concentration-time curve (AUC0-24h, AUC0-t, AUC0-∞) after fed and fasting conditions., Primary Pharmacokinetic endpoint for FIH-CTH120-FI (Not applicable for FIH-CTH120-SAD and FIH-CTH120-MAD).

• Plasma PK parameter calculated using a non-compartmental model: AUC0-24h (h \* ng/mL), AUC0-t (h \* ng/mL) AUC0-∞ (h \* ng/mL)., FIH-CTH120-FI: AUC0-24h on Day 1; AUC0-t, AUC0-∞ where t is the last or the latest timepoint observed|Observed maximum concentration (Cmax) after fed and fasting conditions., Primary Pharmacokinetic endpoint for FIH-CTH120-FI (Not applicable for FIH-CTH120-SAD and FIH-CTH120-MAD)

• Plasma PK parameter calculated using a non-compartmental model: Cmax (ng/mL)., FIH-CTH120-FI: On Day 1 of Period 1, and on Day 14/21/25 of Period 2|Time to observed maximum concentration (tmax) after fed and fasting conditions., Primary Pharmacokinetic endpoint for FIH-CTH120-FI (Not applicable for FIH-CTH120-SAD and FIH-CTH120-MAD)

• Plasma PK parameter calculated using a non-compartmental model: tmax (h)., FIH-CTH120-FI: On Day 1 of Period 1, and on Day 14/21/25 of Period 2
Secondary Outcome Measures: Observed maximum concentration (Cmax)., Secondary Pharmacokinetics endpoints for FIH-CTH120-SAD and FIH-CTH120-MAD (Not applicable for FIH-CTH120-FI).

• Plasma PK parameter calculated using a non-compartmental model: Cmax (ng/mL)., FIH-CTH120-SAD: On Day 1; FIH-CTH120-MAD: on Day 1, and Day 7|Observed minimum concentration (Cmin)., Secondary Pharmacokinetics endpoints for FIH-CTH120-SAD, FIH-CTH120-MAD and FIH-CTH120-FI.

• Plasma PK parameter calculated using a non-compartmental model: Cmin (ng/mL)., FIH-CTH120-SAD: On Day 2; FIH-CTH120-MAD: from Day 2 to Day 7 pre-dose and regularly after the last dose; FIH-CTH120-FI: on Day 2 of Period 1 and Day 15/22/29 of Period 2|Time to observed maximum concentration (tmax)., Secondary Pharmacokinetics endpoints for FIH-CTH120-SAD and FIH-CTH120-MAD (Not applicable for FIH-CTH120-FI).

• Plasma PK parameter calculated using a non-compartmental model: tmax (h)., FIH-CTH120-SAD: On Day 1; FIH-CTH120-MAD: on Day 1, and Day 7|Time to first measurable plasma concentration (tlag)., Secondary Pharmacokinetics endpoints for FIH-CTH120-SAD, FIH-CTH120-MAD and FIH-CTH120-FI.

• Plasma PK parameter calculated using a non-compartmental model: tlag (h)., FIH-CTH120-SAD: On Day 1; FIH-CTH120-MAD: on Day 1, and Day 7; FIH-CTH120-FI: on Day 1 of Period 1 and on Day 14/21/25 of Period 2|Time to last measurable plasma concentration (tlast)., Secondary Pharmacokinetics endpoints for FIH-CTH120-SAD, FIH-CTH120-MAD, and FIH-CTH120-FI.

• Plasma PK parameter calculated using a non-compartmental model: tlast (h)., FIH-CTH120-SAD: On Day 2; FIH-CTH120-MAD: on Day 1, and Day 7; FIH-CTH120-FI: on Day 2 of Period 1 and Day 15/22/29 of Period 2|Area under the concentration-time curve (AUC0-24h, AUC0-t, AUC0-∞)., Secondary Pharmacokinetics endpoints for FIH-CTH120-SAD and FIH-CTH120-MAD (Not applicable for FIH-CTH120-FI).

• Plasma PK parameter calculated using a non-compartmental model: AUC0-24h (h \* ng/mL), AUC0-t (h \* ng/mL) AUC0-∞ (h \* ng/mL)., FIH-CTH120-SAD: AUC0-24h on Day 1; AUC0-t, AUC0-∞ where t is Day 8 (+/- 1 days) or the latest timepoint observed; FIH-CTH120-MAD: "AUC0-24h on Day 1 and Day 7; AUC0-t, AUC0-∞ after last dose, where t is Day 15 (+ 2 days) or the last timepoint observed|Terminal elimination half-life (t1/2)., Secondary Pharmacokinetics endpoints for FIH-CTH120-SAD, FIH-CTH120-MAD, and FIH-CTH120-FI.

• Plasma PK parameter calculated using a non-compartmental model: t1/2 (h)., FIH-CTH120-SAD: from Day 1 to Day 8; FIH-CTH120-MAD: from Day 1 to Day 15; FIH-CTH120-FI: from Day 1 to Day28/35/42|Apparent clearance (CL/F)., Secondary Pharmacokinetics endpoints for FIH-CTH120-SAD, FIH-CTH120-MAD, and FIH-CTH120-FI.

• Plasma PK parameter calculated using a non-compartmental model: CL/F (mL/h \* kg)., FIH-CTH120-SAD: from Day 1 to Day 8; FIH-CTH120-MAD: from Day 1 to Day 15; FIH-CTH120-FI: from Day 1 to Day28/35/42|Apparent volume of distribution: Vd/F., Secondary Pharmacokinetics endpoints for FIH-CTH120-SAD, FIH-CTH120-MAD, and FIH-CTH120-FI.

• Plasma PK parameter calculated using a non-compartmental model: Vd/F (mL/kg)., FIH-CTH120-SAD: from Day 1 to Day 8; FIH-CTH120-MAD: from Day 1 to Day 15; FIH-CTH120-FI: from Day 1 to Day28/35/42|Elimination rate constant (λz)., Secondary Pharmacokinetics endpoints for FIH-CTH120-SAD, FIH-CTH120-MAD, and FIH-CTH120-FI.

• Plasma PK parameter calculated using a non-compartmental model: λz (1/h)., FIH-CTH120-SAD: from Day 1 to Day 8; FIH-CTH120-MAD: from Day 1 to Day 15; FIH-CTH120-FI: from Day 1 to Day28/35/42|Serotonin (5-HT) metabolite profile., Secondary Pharmacodynamic endpoints for FIH-CTH120-SAD and FIH-CTH120-MAD (Not applicable for FIH-CTH120-FI).

Concentrations of 5-Hydroxy indoleacetic acid (5-HIAA) (ng/mL)., FIH-CTH120-SAD: on Day 1 and Day 2; FIH-CTH120-MAD: on Day 1, Day 2, Day 7, and Day 8|Noradrenaline (NA) metabolite profile., Secondary Pharmacodynamic endpoints for FIH-CTH120-SAD and FIH-CTH120-MAD (Not applicable for FIH-CTH120-FI).

Concentrations of 3-Methoxy-4-hydroxyphenylglycol (MHPG) (ng/mL)., FIH-CTH120-SAD: on Day 1 and Day 2; FIH-CTH120-MAD: on Day 1, Day 2, Day 7, and Day 8|Treatment-emergent AEs (TAES)., Secondary Safety and tolerability endpoints (FIH-CTH120-FI).

• AEs will be described in terms of result, frequency, intensity, medical decision, relation with study drug, as well as treatment received and subject retirement, duration, and time elapsed. AEs will also be listed and coded using the MedDRA Dictionary (version 26.0) for the term's codification., FIH-CTH120-FI: from Day 1 to End-of-study. EOS will be on Day 28, or 35 or 42 (±1 day) depending on the length of the washout period determined|Treatment-emergent PSCAs in vital signs: blood pressure (mmHg), Secondary Safety and tolerability endpoints (FIH-CTH120-FI).

• Blood pressure (mmHg) will be measured in the supine position following a 5 min rest., FIH-CTH120-FI: from Day 1 to End-of-study. EOS will be on Day 28, or 35 or 42 (±1 day) depending on the length of the washout period determined|Treatment-emergent PSCAs in vital signs: pulse rate (bpm), Secondary Safety and tolerability endpoints (FIH-CTH120-FI).

• Pulse rate (bpm) will be measured in the supine position following a 5 min rest., FIH-CTH120-FI: from Day 1 to End-of-study. EOS will be on Day 28, or 35 or 42 (±1 day) depending on the length of the washout period determined|Treatment-emergent PSCAs in vital signs: Oral body temperature (ºC), Secondary Safety and tolerability endpoints (FIH-CTH120-FI).

• Oral body temperature (ºC) will be measured using an automated vital sign monitor device., FIH-CTH120-FI: from Day 1 to End-of-study. EOS will be on Day 28, or 35 or 42 (±1 day) depending on the length of the washout period determined|Treatment-emergent PSCAs in ECG values: normal sinus rhythm (NSR), Secondary Safety and tolerability endpoints (FIH-CTH120-FI).

• Computerized 12-lead electrocardiogram (ECG) recordings will be obtained. Each lead shall be recorded for at least 3 beats at a speed of 25 mm/s. Triplicate recordings will be made at the time points evaluated. The following parameter will be recorded: normal sinus rhythm (NSR)., FIH-CTH120-FI: from Day 1 to End-of-study. EOS will be on Day 28, or 35 or 42 (±1 day) depending on the length of the washout period determined|Treatment-emergent PSCAs in ECG values: heart rate (bpm), Secondary Safety and tolerability endpoints (FIH-CTH120-FI).

• Computerized 12-lead electrocardiogram (ECG) recordings will be obtained. Each lead shall be recorded for at least 3 beats at a speed of 25 mm/s. Triplicate recordings will be made at the time points evaluated. The following parameters will be recorded: heart rate (bpm)., FIH-CTH120-FI: from Day 1 to End-of-study. EOS will be on Day 28, or 35 or 42 (±1 day) depending on the length of the washout period determined|Treatment-emergent PSCAs in ECG values: PR interval (ms), Secondary Safety and tolerability endpoints (FIH-CTH120-FI).

• Computerized 12-lead electrocardiogram (ECG) recordings will be obtained. Each lead shall be recorded for at least 3 beats at a speed of 25 mm/s. Triplicate recordings will be made at the time points evaluated. The following parameter will be recorded: PR interval (ms), FIH-CTH120-FI: from Day 1 to End-of-study. EOS will be on Day 28, or 35 or 42 (±1 day) depending on the length of the washout period determined|Treatment-emergent PSCAs in ECG values: QRS duration (ms), Secondary Safety and tolerability endpoints (FIH-CTH120-FI).

• Computerized 12-lead electrocardiogram (ECG) recordings will be obtained. Each lead shall be recorded for at least 3 beats at a speed of 25 mm/s. Triplicate recordings will be made at the time points evaluated. The following parameter will be recorded: QRS duration (ms)., FIH-CTH120-FI: from Day 1 to End-of-study. EOS will be on Day 28, or 35 or 42 (±1 day) depending on the length of the washout period determined|Treatment-emergent PSCAs in ECG values: QT (ms), Secondary Safety and tolerability endpoints (FIH-CTH120-FI).

• Computerized 12-lead electrocardiogram (ECG) recordings will be obtained. Each lead shall be recorded for at least 3 beats at a speed of 25 mm/s. Triplicate recordings will be made at the time points evaluated. The following parameter will be recorded: QT (ms)., FIH-CTH120-FI: from Day 1 to End-of-study. EOS will be on Day 28, or 35 or 42 (±1 day) depending on the length of the washout period determined|Treatment-emergent PSCAs in ECG values: QTcF (ms), Secondary Safety and tolerability endpoints (FIH-CTH120-FI).

• Computerized 12-lead electrocardiogram (ECG) recordings will be obtained. Each lead shall be recorded for at least 3 beats at a speed of 25 mm/s. Triplicate recordings will be made at the time points evaluated. The following parameter will be recorded: QTcF (ms)., FIH-CTH120-FI: from Day 1 to End-of-study. EOS will be on Day 28, or 35 or 42 (±1 day) depending on the length of the washout period determined|Treatment-emergent PSCAs in safety laboratory parameters: haematology, Secondary Safety and tolerability endpoints (FIH-CTH120-FI). The following tests will be performed:

• Haematology: complete blood count (complete blood count \[CBC\]; including haemoglobin, haematocrit, red blood cell \[RBC\], white blood cell (WBC), platelet count, and percent and absolute differential count (neutrophils, lymphocytes, eosinophils, monocytes, basophils, and other cells)., FIH-CTH120-FI: from Day 1 to End-of-study. EOS will be on Day 28, or 35 or 42 (±1 day) depending on the length of the washout period determined|Treatment-emergent PSCAs in safety laboratory parameters: serum chemistry, Secondary Safety and tolerability endpoints (FIH-CTH120-FI). The following tests will be performed:

• Serum chemistry: sodium, potassium, chloride, non-fasting glucose, urea, creatinine, calcium, phosphate, magnesium, total and direct bilirubin, total protein, albumin, ALT, AST, ALP, lactate dehydrogenase., FIH-CTH120-FI: from Day 1 to End-of-study. EOS will be on Day 28, or 35 or 42 (±1 day) depending on the length of the washout period determined|Treatment-emergent PSCAs in safety laboratory parameters: coagulation, Secondary Safety and tolerability endpoints (FIH-CTH120-FI). The following tests will be performed:

• Coagulation parameters: activated partial thromboplastin time (aPTT), PT and INR., FIH-CTH120-FI: from Day 1 to End-of-study. EOS will be on Day 28, or 35 or 42 (±1 day) depending on the length of the washout period determined|Treatment-emergent PSCAs in safety laboratory parameters: urinalysis, Secondary Safety and tolerability endpoints (FIH-CTH120-FI). The following tests will be performed:

• Urinalysis parameters:

* Macroscopic examination: specific gravity, pH, protein, glucose, ketones, blood, bilirubin, leukocyte, urobilinogen, and nitrite.
* Microscopic examination: RBCs, WBCs, epithelial cells, casts, crystals, bacteria, and yeast., FIH-CTH120-FI: from Day 1 to End-of-study. EOS will be on Day 28, or 35 or 42 (±1 day) depending on the length of the washout period determined|Psychometric tests: HADS, Secondary Safety and tolerability endpoints (FIH-CTH120-FI).

• HADS: Self-reported questionnaire used to detect depression and anxiety. It consists of 14 items (7 related to depression and 7 to anxiety) scored using a 4-point Likert scale (each item ranging from 0 to 3). Two scores are generated one for depression and one for anxiety ranging each score ranging from 0 to 21. Higher scores indicate greater levels of anxiety or depression. Both scores can be categorized into: Normality (0-7); Probable case of anxiety or depression (8-10); Case of anxiety or depression (11-21)., FIH-CTH120-FI: On Day -1, Day 2, Day 13/20/27 and Day 15/22/29|Psychometric tests: IMS, Secondary Safety and tolerability endpoints (FIH-CTH120-FI).

• IMS: The IMS is a tool to remotely and quickly track mood changes related to depression and anxiety in the moment. It consists of 22 items, scored between 1 and 7. The total score for this scale is the sum of the scores on all 22 items: ranging from 22 to 154. Lower scores reflect more negative mood states., FIH-CTH120-FI: On Day -1, Day 2, Day 13/20/27 and Day 15/22/29
Other Outcome Measures: Area under the concentration-time curve (AUC0-24h, AUC0-t, AUC0-∞)., Exploratory objective (FIH-CTH120-FI). Plasma pharmacokinetics of the major metabolite of CTH120 after CTH120 single dose administration.

• Plasma PK parameter calculated using a non-compartmental model: AUC0-24h (h \* ng/mL), AUC0-t (h \* ng/mL) AUC0-∞ (h \* ng/mL)., FIH-CTH120-FI: AUC0-24h on Day 1; AUC0-t, AUC0-∞ where t is the last or the latest timepoint observed|Observed maximum concentration (Cmax)., Exploratory objective (FIH-CTH120-FI). Plasma pharmacokinetics of the major metabolite of CTH120 after CTH120 single dose administration.

• Plasma PK parameter calculated using a non-compartmental model: Cmax (ng/mL)., FIH-CTH120-FI: on Day 1 of Period 1 and on Day 14/21/25 of Period 2|Time to observed maximum concentration (tmax)., Exploratory objective (FIH-CTH120-FI). Plasma pharmacokinetics of the major metabolite of CTH120 after CTH120 single dose administration.

• Plasma PK parameter calculated using a non-compartmental model: tmax (h)., FIH-CTH120-FI: on Day 1 of Period 1 and on Day 14/21/25 of Period 2|Observed minimum concentration (Cmin)., Exploratory objective (FIH-CTH120-FI). Plasma pharmacokinetics of the major metabolite of CTH120 after CTH120 single dose administration.

• Plasma PK parameter calculated using a non-compartmental model: Cmin (ng/mL)., FIH-CTH120-FI: on Day 2 of Period 1 and Day 15/22/29 of Period 2|Time to first measurable plasma concentration (tlag)., Exploratory objective (FIH-CTH120-FI). Plasma pharmacokinetics of the major metabolite of CTH120 after CTH120 single dose administration.

• Plasma PK parameter calculated using a non-compartmental model: tlag (h)., FIH-CTH120-FI: on Day 1 of Period 1 and on Day 14/21/25 of Period 2|Time to last measurable plasma concentration (tlast)., Exploratory objective (FIH-CTH120-FI). Plasma pharmacokinetics of the major metabolite of CTH120 after CTH120 single dose administration.

• Plasma PK parameter calculated using a non-compartmental model: tlast (h)., FIH-CTH120-FI: on Day 2 of Period 1 and Day 15/22/29 of Period 2|Terminal elimination half-life (t1/2)., Exploratory objective (FIH-CTH120-FI).

• Plasma PK parameter calculated using a non-compartmental model: t1/2 (h)., FIH-CTH120-FI: from Day 1 to Day28/35/42|Metabolic ratio Cmax (MR Cmax), Exploratory objective (FIH-CTH120-FI). Plasma pharmacokinetics of the major metabolite of CTH120 after CTH120 single dose administration.

• Plasma PK parameter calculated using a non-compartmental model: MR Cmax (n-fold)., FIH-CTH120-FI: from Day 1 to Day28/35/42|Metabolic ratio AUC0-24 (MR AUC0-24), Exploratory objective (FIH-CTH120-FI). Plasma pharmacokinetics of the major metabolite of CTH120 after CTH120 single dose administration.

• Plasma PK parameter calculated using a non-compartmental model: MR AUC0-24 (n-fold), FIH-CTH120-FI: from Day 1 to Day28/35/42|Elimination rate constant (λz), Exploratory objective (FIH-CTH120-FI). Plasma pharmacokinetics of the major metabolite of CTH120 after CTH120 single dose administration.

• Plasma PK parameter calculated using a non-compartmental model: λz (1/h)., FIH-CTH120-FI: from Day 1 to Day28/35/42|Renal clearance (CLr), Exploratory objective (FIH-CTH120-FI). Urine pharmacokinetics of the major metabolite of CTH120 after CTH120 single dose administration.

Renal clearance (L/h), as a Volume/time, calculated as CLr = Ae/PlasmaAUC0-∞, where Ae (µg) is the cumulative amount of unchanged drug excreted into the urine (0-48 h interval) and Plasma AUC0-∞ (ng.h/mL) is the area under the plasma concentration-time curve from time zero to infinity., FIH-CTH120-FI: from Day 1 to Day28/35/42|Amount excreted: absolute value as Ae, Exploratory objective (FIH-CTH120-FI). Urine pharmacokinetics of the major metabolite of CTH120 after CTH120 single dose administration.

• The excreted amount will be calculated as absolute value as Ae: cumulative amount of unchanged drug excreted into the urine (interval) (µg)., FIH-CTH120-FI: from Day 1 to Day28/35/42|Amount excreted: relative to dose as fe/F, Exploratory objective (FIH-CTH120-FI). Urine pharmacokinetics of the major metabolite of CTH120 after CTH120 single dose administration.

• The excreted amount will be calculated as relative to dose as fe/F: fraction of the oral administered drug excreted into the urine (%)., FIH-CTH120-FI: from Day 1 to Day28/35/42|Urinary excretion rate (UER), Exploratory objective (FIH-CTH120-FI). Urine pharmacokinetics of the major metabolite of CTH120 after CTH120 single dose administration.

The urinary excretion rate (μg/h) is the product of the urine flow rate (mL/h) and the urine analyte concentration (ng/mL), where:

* Urine flow rate (UFR) is the quotient between the Urine volume (mL) and the time interval (h), where urine volume is the total urine volume collected in the time interval (mL).
* Urine analyte concentration: concentration of the analyte in urine (ng/mL)., FIH-CTH120-FI: from Day 1 to Day28/35/42|Urine elimination rate constant (h-1), Exploratory objective (FIH-CTH120-FI). Urine pharmacokinetics of the major metabolite of CTH120 after CTH120 single dose administration.

• Urine elimination rate constant (h-1): calculated as the slope (semilog plot) of the cumulative amount of drug excreted after each collection interval against the median of the collection interval. Nominal or actual times can be used as appropriate., FIH-CTH120-FI: from Day 1 to Day28/35/42