Clinical trial NCT06480968: CTH120 First-in-Human Study: Single and Multiple Ascending Doses and Potential Food Interaction
Official title: Safety and Tolerability of CTH120, First-in-human Phase I Study Encompassing Three Parts: Single and Multiple Ascending Doses and Potential Food Interaction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Fragile X Syndrome
Keywords: Fragile X Syndrome
FXS
Fragile X
Neurodevelopmental Disorders
Central Nervous System Diseases
Intellectual Disability
Neurobehavioral Manifestations
Genetic Diseases, X-Linked
Congenital Abnormalities
Orphan Diseases
Rare Diseases
Lead sponsor: Connecta Therapeutics, S.L.
Sponsor class: INDUSTRY
Collaborators: name: Hospital del Mar Research Institute (IMIM)
name: Adknoma Health Research
name: Ministry of Science and Innovation, Spain
First posted: 2024-07-01
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: FIH-CTH120-SAD: Prospective, monocentre, double-blind, randomized, placebo-controlled, subsequent-group, Phase I investigation to assess the safety, tolerability and pharmacokinetics of CTH120 administered orally in single ascending doses.

FIH-CTH120-MAD: Prospective, monocentre, double-blind, randomized, placebo-controlled, subsequent-groups, Phase I investigation to assess the safety, tolerability and pharmacokinetics of CTH120 administered orally in multiple ascending doses.

FIH-CTH120-FI: Prospective, open-label single dose, two-condition (fed versus fasting), two sequences, crossover Phase I investigation to assess the effects of food on the bioavailability of CTH120.
Primary purpose: TREATMENT

Brief 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.

Detailed description: This trial is divided in three parts: FIH-CTH120-SAD (Single Ascending Doses), FIH-CTH120-MAD (Multiple Ascending Doses) and FIH-CTH120-FI (Food Interaction). FIH-CTH120-SAD will start first. The start of FIH-CTH120-MAD will await the results of at least three cohorts from the FIH-CTH120-SAD study before initiated. The starting dose of the FIH-CTH120-MAD will have been shown to be well tolerated in FIH-CTH120-SAD. FIH-CTH120-FI will be the last to start.

Eligibility criteria: Inclusion Criteria:

* Healthy male subjects: As the effect of the study drug on sperm is still unknown, male subjects should refrain from donating sperm or plan a pregnancy with their partner throughout the study and after 90 days after the trial and must report immediately to the study doctor if its partner becomes pregnant during the study and during 90 days after the study. The male subject will have to use double- barrier contraceptive methods: male condoms and spermicide.
* Healthy female subjects of non-child-bearing potential: females may be accepted if they are documented to be surgically sterile i.e., hysterectomy, tubal ligation or post-menopausal with a negative pregnancy test.
* Age ≥ 18 and ≤ 55 years.
* Weight ≥ 50 kg and ≤ 100 kg.
* Body mass index (BMI) ≥ 18 and ≤ 30.
* Negative serum pregnancy test (women only).
* Non-smoking.
* No history of or ongoing clinically relevant diseases or conditions.
* No clinically relevant findings in physical examination, vital signs (blood pressure, heart rate and body temperature), ECG and safety laboratory parameters that should be within normal ranges or considered as non-clinically relevant by the investigator.
* Able/willing to accept restrictions regarding diet, physical exercise, and consumption of alcohol and/or xanthine containing items during the duration of the trial including when out of CRU.
* Able to read Spanish or Catalan and adhere to study requirements.
* Not under any administrative or legal supervision.
* Signed informed consent prior to any study-mandated procedure.

Exclusion Criteria:

* Women of child-bearing potential.
* Life-time substance use disorders (SUD) according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5).
* Recreational use of drugs of abuse within the last month prior to study drug administration (verified by hair testing).
* Positive blood or urine test for drugs of abuse or alcohol breath test prior to study drug administration.
* Life-time history of mental diseases.
* History of anxiety or depression not completely recovered within 12 months prior to study drug administration, as assessed by the Dual Diagnosis Screening Interview (DDSI).
* Clinically relevant cognitive impairment preventing the administration of the psychometric tests.
* Any other clinically relevant disease or condition that in the judgment of the investigator might interfere with the subject's ability to comply with study procedures or requirements and/or bias the interpretation of the study results and/or jeopardize the subject's safety.
* Ongoing gastrointestinal diseases or history of gastrointestinal surgery affecting absorption.
* Subjects with a clinically significant disease within one month prior to study drug administration.
* Any clinically relevant findings in physical examination, vital signs, ECG and safety laboratory parameters.
* A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval \>450 ms).
* A history of additional risk factors for TdP (e.g., heart failure, hypokalaemia, family history of Long QT Syndrome).
* The use of concomitant medications that prolong the QT/QTc interval.
* Positive hepatitis or HIV test.
* Known hypersensitivity to drug or drug excipients.
* Use of drugs known to induce or inhibit hepatic drug metabolism within one month prior to study administration or during the study and use of citrus juice during the study.
* Any prescription or over-the-counter (OTC) product including herbal, homeopathic, vitamins, minerals and nutritional supplements within 2 weeks (or more, considering the elimination half-life of the product) prior to study drug administration.
* Donation of blood or plasma within one month prior to study drug administration or transfusion of blood or plasma for medical/surgical reasons or intention to donate blood or plasma within one month after study drug administration.
* History of inadequate venous access and/or experience of difficulty donating blood.
* Not able/not willing to accept restrictions regarding diet, physical exercise, and consumption of alcohol and/or xanthine containing items when out of CRU.
* Subject included in a clinical study within 3 months prior to study drug administration.
* Subject already included in other parts of this study.

Primary outcomes:
measure: Treatment-emergent adverse events (TEAEs).
timeFrame: 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
measure: Treatment-emergent potentially clinically significant abnormalities (PSCAs) in blood pressure (mmHg)
timeFrame: 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
measure: Treatment-emergent potentially clinically significant abnormalities (PSCAs) in pulse rate (bpm)
timeFrame: 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
measure: Treatment-emergent potentially clinically significant abnormalities (PSCAs) in oral body temperature (ºC)
timeFrame: 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
measure: Treatment-emergent potentially clinically significant abnormalities (PSCAs) in electrocardiogram (ECG) values: normal sinus rhythm (NSR)
timeFrame: 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
measure: Treatment-emergent potentially clinically significant abnormalities (PSCAs) in electrocardiogram (ECG) values: heart rate (bpm)
timeFrame: 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
measure: Treatment-emergent potentially clinically significant abnormalities (PSCAs) in electrocardiogram (ECG) values: PR interval (ms)
timeFrame: 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
measure: Treatment-emergent potentially clinically significant abnormalities (PSCAs) in electrocardiogram (ECG) values: QRS duration (ms)
timeFrame: 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
measure: Treatment-emergent potentially clinically significant abnormalities (PSCAs) in electrocardiogram (ECG) values: QT (ms)
timeFrame: 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
measure: Treatment-emergent potentially clinically significant abnormalities (PSCAs) in electrocardiogram (ECG) values: QTcF (ms)
timeFrame: 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
measure: Treatment-emergent potentially clinically significant abnormalities (PSCAs) in safety laboratory parameters: haematology
timeFrame: 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
measure: Treatment-emergent potentially clinically significant abnormalities (PSCAs) in safety laboratory parameters: serum chemistry
timeFrame: 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
measure: Treatment-emergent potentially clinically significant abnormalities (PSCAs) in safety laboratory parameters: coagulation
timeFrame: 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
measure: Treatment-emergent potentially clinically significant abnormalities (PSCAs) in safety laboratory parameters: urinalysis
timeFrame: 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
measure: Psychometric tests: Hospital Anxiety/Depression rating Scale (HADS)
timeFrame: FIH-CTH120-SAD: on Day -1 and Day 2; FIH-CTH120-MAD: on Day -1, Day 1, and Day 7
measure: Psychometric tests:Immediate Mood Scaler (IMS).
timeFrame: FIH-CTH120-SAD: on Day -1 and Day 2; FIH-CTH120-MAD: on Day -1, Day 1, and Day 7
measure: Area under the concentration-time curve (AUC0-24h, AUC0-t, AUC0-∞) after fed and fasting conditions.
timeFrame: FIH-CTH120-FI: AUC0-24h on Day 1; AUC0-t, AUC0-∞ where t is the last or the latest timepoint observed
measure: Observed maximum concentration (Cmax) after fed and fasting conditions.
timeFrame: FIH-CTH120-FI: On Day 1 of Period 1, and on Day 14/21/25 of Period 2
measure: Time to observed maximum concentration (tmax) after fed and fasting conditions.
timeFrame: FIH-CTH120-FI: On Day 1 of Period 1, and on Day 14/21/25 of Period 2
Secondary outcomes:
measure: Observed maximum concentration (Cmax).
timeFrame: FIH-CTH120-SAD: On Day 1; FIH-CTH120-MAD: on Day 1, and Day 7
measure: Observed minimum concentration (Cmin).
timeFrame: 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
measure: Time to observed maximum concentration (tmax).
timeFrame: FIH-CTH120-SAD: On Day 1; FIH-CTH120-MAD: on Day 1, and Day 7
measure: Time to first measurable plasma concentration (tlag).
timeFrame: 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
measure: Time to last measurable plasma concentration (tlast).
timeFrame: 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
measure: Area under the concentration-time curve (AUC0-24h, AUC0-t, AUC0-∞).
timeFrame: 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
measure: Terminal elimination half-life (t1/2).
timeFrame: 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
measure: Apparent clearance (CL/F).
timeFrame: 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
measure: Apparent volume of distribution: Vd/F.
timeFrame: 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
measure: Elimination rate constant (λz).
timeFrame: 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
measure: Serotonin (5-HT) metabolite profile.
timeFrame: FIH-CTH120-SAD: on Day 1 and Day 2; FIH-CTH120-MAD: on Day 1, Day 2, Day 7, and Day 8
measure: Noradrenaline (NA) metabolite profile.
timeFrame: FIH-CTH120-SAD: on Day 1 and Day 2; FIH-CTH120-MAD: on Day 1, Day 2, Day 7, and Day 8
measure: Treatment-emergent AEs (TAES).
timeFrame: 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
measure: Treatment-emergent PSCAs in vital signs: blood pressure (mmHg)
timeFrame: 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
measure: Treatment-emergent PSCAs in vital signs: pulse rate (bpm)
timeFrame: 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
measure: Treatment-emergent PSCAs in vital signs: Oral body temperature (ºC)
timeFrame: 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
measure: Treatment-emergent PSCAs in ECG values: normal sinus rhythm (NSR)
timeFrame: 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
measure: Treatment-emergent PSCAs in ECG values: heart rate (bpm)
timeFrame: 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
measure: Treatment-emergent PSCAs in ECG values: PR interval (ms)
timeFrame: 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
measure: Treatment-emergent PSCAs in ECG values: QRS duration (ms)
timeFrame: 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
measure: Treatment-emergent PSCAs in ECG values: QT (ms)
timeFrame: 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
measure: Treatment-emergent PSCAs in ECG values: QTcF (ms)
timeFrame: 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
measure: Treatment-emergent PSCAs in safety laboratory parameters: haematology
timeFrame: 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
measure: Treatment-emergent PSCAs in safety laboratory parameters: serum chemistry
timeFrame: 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
measure: Treatment-emergent PSCAs in safety laboratory parameters: coagulation
timeFrame: 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
measure: Treatment-emergent PSCAs in safety laboratory parameters: urinalysis
timeFrame: 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
measure: Psychometric tests: HADS
timeFrame: FIH-CTH120-FI: On Day -1, Day 2, Day 13/20/27 and Day 15/22/29
measure: Psychometric tests: IMS
timeFrame: FIH-CTH120-FI: On Day -1, Day 2, Day 13/20/27 and Day 15/22/29
Other outcomes:
measure: Area under the concentration-time curve (AUC0-24h, AUC0-t, AUC0-∞).
timeFrame: FIH-CTH120-FI: AUC0-24h on Day 1; AUC0-t, AUC0-∞ where t is the last or the latest timepoint observed
measure: Observed maximum concentration (Cmax).
timeFrame: FIH-CTH120-FI: on Day 1 of Period 1 and on Day 14/21/25 of Period 2
measure: Time to observed maximum concentration (tmax).
timeFrame: FIH-CTH120-FI: on Day 1 of Period 1 and on Day 14/21/25 of Period 2
measure: Observed minimum concentration (Cmin).
timeFrame: FIH-CTH120-FI: on Day 2 of Period 1 and Day 15/22/29 of Period 2
measure: Time to first measurable plasma concentration (tlag).
timeFrame: FIH-CTH120-FI: on Day 1 of Period 1 and on Day 14/21/25 of Period 2
measure: Time to last measurable plasma concentration (tlast).
timeFrame: FIH-CTH120-FI: on Day 2 of Period 1 and Day 15/22/29 of Period 2
measure: Terminal elimination half-life (t1/2).
timeFrame: FIH-CTH120-FI: from Day 1 to Day28/35/42
measure: Metabolic ratio Cmax (MR Cmax)
timeFrame: FIH-CTH120-FI: from Day 1 to Day28/35/42
measure: Metabolic ratio AUC0-24 (MR AUC0-24)
timeFrame: FIH-CTH120-FI: from Day 1 to Day28/35/42
measure: Elimination rate constant (λz)
timeFrame: FIH-CTH120-FI: from Day 1 to Day28/35/42
measure: Renal clearance (CLr)
timeFrame: FIH-CTH120-FI: from Day 1 to Day28/35/42
measure: Amount excreted: absolute value as Ae
timeFrame: FIH-CTH120-FI: from Day 1 to Day28/35/42
measure: Amount excreted: relative to dose as fe/F
timeFrame: FIH-CTH120-FI: from Day 1 to Day28/35/42
measure: Urinary excretion rate (UER)
timeFrame: FIH-CTH120-FI: from Day 1 to Day28/35/42
measure: Urine elimination rate constant (h-1)
timeFrame: FIH-CTH120-FI: from Day 1 to Day28/35/42
Locations:
city: Barcelona
country: Spain
facility: Hospital del Mar Medical Research Institute (IMIM)
Study officials:
affiliation: Hospital del Mar Medical Research Institute (IMIM)
name: Rafael De la Torre, Pharm, PhD
role: PRINCIPAL_INVESTIGATOR
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