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CTx-1301 Comparative Bioavailability Study

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ClinicalTrials.gov Identifier: NCT04138498
Recruitment Status : Completed
First Posted : October 24, 2019
Results First Posted : April 8, 2021
Last Update Posted : April 8, 2021
Sponsor:
Information provided by (Responsible Party):
Cingulate Therapeutics

Brief Summary:
The primary purpose of this study is to compare the bioavailability of CTx-1301 (dexmethylphenidate) to the registered listed drug, Focalin XR and to evaluate dose proportionality of CTx-1301. In addition, this study seeks to characterize the pharmacokinetics of dexmethylphenidate and evaluate the safety and tolerability of CTx-1301.

Condition or disease Intervention/treatment Phase
ADHD Drug: Dexmethylphenidate 5 Mg Oral Capsule, Extended Release Drug: Dexmethylphenidate 6.25 mg Tablet Drug: Dexmethylphenidate 40 Mg Oral Capsule, Extended Release Drug: Dexmethylphenidate 50 mg Tablet Phase 1 Phase 2

Detailed Description:

The study will comprise of a randomized, single-dose, four-sequence, four-period, in-clinic crossover study in approximately 36 adult ADHD subjects. All subjects considered eligible at Screening will proceed to tolerability test day, dosing 40 mg Focalin XR to evaluate safety and tolerability of the higher dose of d-MPH. If subject is able to safely tolerate the test dose, and meets all inclusion/exclusion criteria, they will be considered eligible for randomization into the study. All subjects will be randomized to receive four treatments throughout the course of the study; one CTx-1301 trimodal d-MPH tablet containing 6.25 mg d-MPH, one Focalin 5 mg XR capsule, one CTx-1301 50 mg tablet, and one 40 mg Focalin XR capsule. Administration of study drug will occur only on Assessment Days; no study drug will be administered during screening or unscheduled days (USVs).

The lowest and highest doses of CTx-1301 (dexmethylphenidate, 6.25 and 50 mg) were selected to bridge to the lowest and highest doses of Focalin XR (dexmethylphenidate, 5 and 40 mg) in this comparative BA study.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 45 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Single-dose, Four-sequence, Four-period, Crossover Study in Adult ADHD Subjects to Establish Safety, Tolerability, and Comparative Bioavailability of CTx-1301 (Dexmethylphenidate) to Focalin XR™ Under Fasted Conditions
Actual Study Start Date : December 6, 2019
Actual Primary Completion Date : March 6, 2020
Actual Study Completion Date : March 6, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Sequence 1 (ADBC)
Subjects in sequence ADBC will receive study treatments in the following order: Focalin XR 5 mg capsule, CTx-1301 50 mg tablet, CTx-1301 6.25 mg tablet, Focalin XR 40 mg capsule.
Drug: Dexmethylphenidate 5 Mg Oral Capsule, Extended Release
Reference listed drug (RLD) for comparative BA evaluation
Other Name: Focalin XR (dexmethylphenidate) 5 mg Capsule

Drug: Dexmethylphenidate 6.25 mg Tablet
Experimental drug for comparative BA evaluation
Other Name: CTx-1301 (dexmethylphenidate) 6.25 mg Tablet

Drug: Dexmethylphenidate 40 Mg Oral Capsule, Extended Release
Reference listed drug (RLD) for comparative BA evaluation
Other Name: Focalin XR (dexmethylphenidate) 40 mg capsule

Drug: Dexmethylphenidate 50 mg Tablet
Experimental drug for comparative BA evaluation
Other Name: CTx-1301 (dexmethylphenidate) 50 mg tablet

Experimental: Sequence 2 (BACD)
Subjects in sequence BACD will receive study treatments in the following order: CTx-1301 6.25 mg tablet, Focalin XR 5 mg capsule, Focalin XR 40 mg capsule, CTx-1301 50 mg tablet.
Drug: Dexmethylphenidate 5 Mg Oral Capsule, Extended Release
Reference listed drug (RLD) for comparative BA evaluation
Other Name: Focalin XR (dexmethylphenidate) 5 mg Capsule

Drug: Dexmethylphenidate 6.25 mg Tablet
Experimental drug for comparative BA evaluation
Other Name: CTx-1301 (dexmethylphenidate) 6.25 mg Tablet

Drug: Dexmethylphenidate 40 Mg Oral Capsule, Extended Release
Reference listed drug (RLD) for comparative BA evaluation
Other Name: Focalin XR (dexmethylphenidate) 40 mg capsule

Drug: Dexmethylphenidate 50 mg Tablet
Experimental drug for comparative BA evaluation
Other Name: CTx-1301 (dexmethylphenidate) 50 mg tablet

Experimental: Sequence 3 (CBDA)
Subjects in sequence CBDA will receive study treatments in the following order: Focalin XR 40 mg capsule, CTx-1301 6.25 mg tablet, CTx-1301 50 mg tablet, Focalin XR 5 mg capsule.
Drug: Dexmethylphenidate 5 Mg Oral Capsule, Extended Release
Reference listed drug (RLD) for comparative BA evaluation
Other Name: Focalin XR (dexmethylphenidate) 5 mg Capsule

Drug: Dexmethylphenidate 6.25 mg Tablet
Experimental drug for comparative BA evaluation
Other Name: CTx-1301 (dexmethylphenidate) 6.25 mg Tablet

Drug: Dexmethylphenidate 40 Mg Oral Capsule, Extended Release
Reference listed drug (RLD) for comparative BA evaluation
Other Name: Focalin XR (dexmethylphenidate) 40 mg capsule

Drug: Dexmethylphenidate 50 mg Tablet
Experimental drug for comparative BA evaluation
Other Name: CTx-1301 (dexmethylphenidate) 50 mg tablet

Experimental: Sequence 4 (DCAB)
Subjects in sequence DCAB will receive study treatments in the following order: CTx-1301 50 mg tablet, Focalin XR 40 mg capsule, Focalin XR 5 mg capsule, CTx-1301 6.25 mg tablet.
Drug: Dexmethylphenidate 5 Mg Oral Capsule, Extended Release
Reference listed drug (RLD) for comparative BA evaluation
Other Name: Focalin XR (dexmethylphenidate) 5 mg Capsule

Drug: Dexmethylphenidate 6.25 mg Tablet
Experimental drug for comparative BA evaluation
Other Name: CTx-1301 (dexmethylphenidate) 6.25 mg Tablet

Drug: Dexmethylphenidate 40 Mg Oral Capsule, Extended Release
Reference listed drug (RLD) for comparative BA evaluation
Other Name: Focalin XR (dexmethylphenidate) 40 mg capsule

Drug: Dexmethylphenidate 50 mg Tablet
Experimental drug for comparative BA evaluation
Other Name: CTx-1301 (dexmethylphenidate) 50 mg tablet




Primary Outcome Measures :
  1. Cmax [ Time Frame: Hours 0 to 28 ]
    d-MPH Plasma concentration

  2. AUC(0-infinity) [ Time Frame: Hours 0 to 28 ]
    Area under the curve from time 0 extrapolated to infinite time

  3. AUC(Last) [ Time Frame: Hours 0 to 28 ]
    AUC from time 0 to the last measurable concentration


Secondary Outcome Measures :
  1. Partial AUCs [ Time Frame: Hours 0 to 28 ]
    AUC from Hours 0-3, 3-6, 6-9, 9-12, and 12 to 16

  2. K [ Time Frame: Hours 0 to 28 ]
    Rate at which a drug is removed from the system

  3. Half-life [ Time Frame: Hours 0 to 28 ]
    Time (Hours) it takes for the concentration of the drug in plasma to be reduced by 50%

  4. Tmax [ Time Frame: Hours 0 to 28 ]
    Time (Hours) after administration of a drug when the maximum plasma concentration is reached

  5. Tlag [ Time Frame: Hours 0 to 28 ]
    Delay (hours) between the time of dosing and time of appearance of concentration in the sampling

  6. Incidence of Treatment-Emergent Adverse Events [ Time Frame: Day 0 to Day 10 ]
    TEAEs will be measured from Day 0 to Day 10 (End of Study)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Gender

    a. Male or Female

  2. Age

    a. Aged between 18 and 55 years inclusive.

  3. Weight and BMI

    1. Body weight ≥ 50 kg
    2. BMI ≥ 18 and ≤ 35
  4. Compliance

    1. Understands and is willing, able and likely to comply with all study procedures and restrictions.
    2. If sexually active, male subjects must use the double-barrier method (condom and spermicide) for birth control during the study and for 90 days following the last administration of study drug.
    3. If sexually active, female subjects of child-bearing potential must use an acceptable method of contraception, including abstinence from heterosexual intercourse, hormonal contraceptives, intrauterine device (IUD) with or without hormones, or double-barrier method (e.g. condom and spermicide), during the study and for 30 days following the last administration of study drug.
    4. Male subjects must agree not to donate sperm during the study and for 90 days following the last administration of study drug.
    5. Female subjects must agree not to donate eggs during the study and for 30 days following the last administration of study drug.
  5. Consent a. Demonstrates understanding of the study and willingness to participate as evidenced by voluntary written informed consent (signed and dated) obtained before any study-related activities are performed.
  6. Indication

    1. Subject must report history of diagnosis of ADHD.
    2. If subject is currently taking stimulant medication, they must be willing and able to safely abstain from any other ADHD treatment during 96 hrs. prior to check-in on Day -4 and through the complete duration of the study.
  7. General Health

    1. Good general health (in the opinion of an investigator) with no clinically significant or relevant abnormalities on medical history or physical examination which could affect the safety of the subject or study data.
    2. No vomiting or fever within 24-hours of check-in at Day -4
    3. Subject has sufficient venous access to allow cannulation and/or venipuncture to obtain the required volume of blood for this study.
    4. Subject must currently be taking or previously have taken a stimulant medication for ADHD.
  8. Smoking/Caffeine/Alcohol

    1. Subject must be able to refrain from smoking cigarettes 1 hour prior to dosing and 7 hours after dosing on dosing days. Subject must agree not to smoke more than one cigarette per hour, not to exceed 10 cigarettes per day.
    2. Subject must be able to refrain from caffeine for 10 hours prior to check-in at Day -4 and for the duration of the study.
    3. Subject must be able to refrain from using alcohol 48 hrs. prior to Day -4 and for the duration of the study.
  9. ADHD Medication History

    1. Subject's medication history suggests they will be able to tolerate a 40 mg dose of dexmethylphenidate.
    2. Subject must demonstrate tolerability of dexmethylphenidate assessed by tolerability day/test dose of 40 mg Focalin XR as evaluated by the investigator.

Exclusion Criteria:

  1. Medical History

    1. Current and/or recurrent disease or illness that, in the opinion of an investigator, could affect the study conduct, study outcome, subject safety, or pharmacokinetic (PK) assessments (e.g., hepatic disorders, renal insufficiency, non-self-limiting gastrointestinal disorders, congestive heart failure).
    2. Current and/or previous history of any other serious, severe or unstable psychiatric illness which in the opinion of the investigator, may require treatment (e.g. anxiety, psychosis, mood disorder, motor tics or suicidality) or make the subject unlikely to fully complete the study, and/or any condition that presents undue risk from the study medication or procedures.
    3. Subject cannot have suicidal thoughts within the last 6 months as supported by the Columbia Suicide Severity Rating Scale (C-SSRS).
    4. Positive test results for Human Immunodeficiency Virus (HIV)-1/HIV-2 antibodies, Hepatitis B surface antigen (HBsAg) or Hepatitis C virus antibody (HCVAb).
    5. A family history of sudden cardiac or unexplained death.
    6. Any condition or abnormal laboratory finding that could result in harm to the subject, affect the outcome of the study, or suggest unstable medical illness.
    7. As a result of the MINI, medical history, physical examination, and/or screening investigations (including ECG results, vital signs and/or laboratory abnormality), an Investigator considers the subject disqualified for the study.
    8. Subject plans to undergo elective procedures/surgery at any time during the study.
    9. Subject has had surgery within the past 90 days.
    10. Subject of child-bearing potential is pregnant or planning to become pregnant during the duration of the study or within 30 days of the end of the study.
    11. Subject is breast-feeding during the study or within 30 days of the study.
  2. Medications

    a. Subject has taken any medication that, in the opinion of an Investigator, has been shown to alter the PK of d-MPH.

    b. Use of any prescription medication within 14 days prior to Day -3 (ADHD medications must be discontinued at least 96 hours prior to check-in at Day -4), and/or use of any OTC medications (such as antacids, vitamins, minerals, dietary/herbal preparations, and nutritional supplements) within 7 days prior to Day -3 unless jointly approved by an Investigator and Sponsor.

    i. Subjects are permitted to take hormonal contraceptives and hormone replacement therapy at acceptable levels if stable at least 30 days prior to Day -4, through the duration of the study, and for 30 days after the study ends.

    ii. Acetaminophen (up to 2 grams per day) may be used during the study under the direction of the Investigator.

    iii. On a case-by-case basis, an Investigator is permitted to allow the use of certain concomitant medications, for example, to treat an AE, as long as an Investigator determines that the medication will not affect the subject's safety or study integrity (eg, topical medications).

  3. Alcohol/Substance Abuse

    1. Recent history (within the last year) of alcohol or other substance abuse.
    2. Subject has positive breath alcohol test or urine test for drugs of abuse at screening or check-in (prescribed ADHD medication is acceptable during screening but must be stopped at least 96 hrs prior to check in at Day -4). Note: At the discretion of an Investigator, the tests may be repeated. If THC is positive at screening or check-in, a cannabis intoxication evaluation will be done by an investigator at check-in only; inclusion will be at the investigator's discretion, due to the slow release of THC from adipose tissue.
  4. Smoking

    a. Subject regularly smokes more than 10 cigarettes/day (or other nicotine-containing products) or Subject has recently discontinued smoking (within the last 3 months)

  5. Allergy/Intolerance

    a. Subject has a history of allergy to d-MPH, to any component of the dosage form, or any other allergy, which, in the opinion of an Investigator, contraindicates their participation.

  6. Clinical Studies

    1. Participation in another investigational product study (inclusive of final post-study examination) or receipt of an investigational drug within the 30 days before screening day.
    2. Previous participation in this study.
  7. Personnel

    a. An employee of the sponsor, study site, or members of their immediate family.

  8. Blood

    1. Subject has donated blood, plasma, or experienced significant blood loss (excess of 500 ml) within 3 months of screening and for the duration of the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04138498


Locations
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United States, Kansas
Vince & Associates
Overland Park, Kansas, United States, 66212
Sponsors and Collaborators
Cingulate Therapeutics
Investigators
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Study Director: Matt Brams, MD Sponsor Medical Officer
  Study Documents (Full-Text)

Documents provided by Cingulate Therapeutics:
Study Protocol  [PDF] January 16, 2020
Statistical Analysis Plan  [PDF] February 12, 2020

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Responsible Party: Cingulate Therapeutics
ClinicalTrials.gov Identifier: NCT04138498    
Other Study ID Numbers: CTx-1301-001
First Posted: October 24, 2019    Key Record Dates
Results First Posted: April 8, 2021
Last Update Posted: April 8, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Cingulate Therapeutics:
ADHD
bioavailability
dexmethylphenidate
BA study
dMPH
d-MPH
Additional relevant MeSH terms:
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Dexmethylphenidate Hydrochloride
Central Nervous System Stimulants
Physiological Effects of Drugs
Dopamine Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Dopamine Agents
Neurotransmitter Agents