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A Study in Healthy Subjects to Assess the Safety, Tolerability, PK and PD of HTL0030310

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ClinicalTrials.gov Identifier: NCT03847207
Recruitment Status : Active, not recruiting
First Posted : February 20, 2019
Last Update Posted : August 8, 2019
Sponsor:
Information provided by (Responsible Party):
Heptares Therapeutics Limited

Brief Summary:
A Phase 1, first in human, three-part, single centre study to assess the safety, tolerability, PK and PD of single ascending subcutaneous doses of HTL0030310 in healthy subjects

Condition or disease Intervention/treatment Phase
Healthy Drug: HTL0030310 Drug: Pasireotide Drug: Placebo Phase 1

Detailed Description:
This is a first in human, three part study with the objective to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of single ascending subcutaneous doses of HTL0030310 in healthy subjects. Part 1 is a double-blind, placebo-controlled, randomised study assessing single ascending doses of HTL0030310. Part 2 is a site-blind (sponsor unblinded), placebo-controlled, part-randomised, fixed-sequence, single-dose, 4-period study assessing the PD of a positive control, pasireotide, following administration of challenge agents. Part 3 is a double-blind, placebo-controlled, part-randomised, fixed-sequence, single-dose, HTL0030310 proof of pharmacological effect study, where PD effects of HTL0030310 will be investigated following administration of challenge agents. The challenge agents administered in this study will be: oral glucose tolerance test (OGTT), Growth hormone-releasing hormone (GHRH), and corticotrophin releasing hormone (CRH) combined with desmopressin.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Three-Part Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Ascending Subcutaneous Doses of HTL0030310 in Healthy Subjects
Actual Study Start Date : February 13, 2019
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : April 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Pasireotide

Arm Intervention/treatment
Experimental: Part 1 Single Ascending Dose
Eight subjects in up to 8 cohorts will be dosed. A single subcutaneous injection of HTL0030310 or placebo will be administered. In each cohort, 6 subjects will receive HTL0030310 and 2 subjects will receive placebo.
Drug: HTL0030310
Solution for Subcutaneous injection

Drug: Placebo
Matching placebo Solution

Experimental: Part 2 Pasireotide PD Assessment
Sixteen subjects in 2 cohorts (8 subjects per cohort) will be dosed on 4 occasions. Within each cohort, 4 subjects will be randomised to active dosing with CRH with desmopressin, GHRH and OGTT challenge and 4 subjects will be randomised to placebo dosing with CRH with desmopressin, GHRH and OGTT challenge.
Drug: Pasireotide
Pasireotide 600 μg for subcutaneous injection

Drug: Placebo
Matching placebo Solution

Experimental: Part 3 Proof of Pharmacological Effect
Up to 80 subjects in 4 cohorts (up to 20 subjects per cohort) will be dosed in up to 3 study periods. In each period, subjects will receive active drug or placebo with GHRH, OGTT and CRH with desmopressin (optional).
Drug: HTL0030310
Solution for Subcutaneous injection

Drug: Placebo
Matching placebo Solution




Primary Outcome Measures :
  1. Part 1: Number of treatment related adverse events (as determined by abnormal clinical laboratory tests, vitals signs, ECG parameters, Holter ECG parameters and injection site reactions) [ Time Frame: Admission up to 8 days post dose ]
    Safety and Tolerability

  2. Part 2 and Part 3 Area under the effect time curve (EAUC) 1) for insulin, glucose, glucagon, GLP1, C-peptide and GIP level 2) for GH 3) ACTH and cortisol [ Time Frame: Predose up to 4 hours post dose ]
    Pharmacodynamics

  3. Part 2 and Part 3 Maximum observed effect (EMax) 1) for insulin, glucose, glucagon, GLP1, C-peptide and GIP level 2) for GH 3) ACTH and cortisol [ Time Frame: Predose up to 4 hours post dose ]
    Pharmacodynamics

  4. Part 2 and Part 3 Time to reach Maximum observed effect (TEMax) 1) for insulin, glucose, glucagon, GLP1, C-peptide and GIP level 2) for GH 3) ACTH and cortisol [ Time Frame: Predose up to 4 hours post dose ]
    Pharmacodynamics


Secondary Outcome Measures :
  1. Part 1 Maximum observed plasma concentration (Cmax) of single subcutaneous doses of HTL0030310 [ Time Frame: Pre dose to 144 hours post dose ]
    Pharmacokinetics

  2. Part 1 Time to reach Maximum observed plasma concentration (Tmax) of single subcutaneous doses of HTL0030310 [ Time Frame: Pre dose to 144 hours post dose ]
    Pharmacokinetics

  3. Part 1 Area under the curve (AUC) of single subcutaneous doses of HTL0030310 [ Time Frame: Pre dose to 144 hours post dose ]
    Pharmacokinetics

  4. Part 2 Maximum observed plasma concentration (Cmax) of single subcutaneous doses of pasireotide [ Time Frame: Predose to 24 hours postdose ]
    Pharmacokinetics

  5. Part 2 Time to reach Maximum observed plasma concentration (Tmax) of single subcutaneous doses of pasireotide [ Time Frame: Predose to 24 hours postdose ]
    Pharmacokinetics

  6. Part 2 Area under the curve (AUC) of single subcutaneous doses of pasireotide [ Time Frame: Predose to 24 hours postdose ]
    Pharmacokinetics

  7. Part 3: Number of treatment related adverse events (as determined by abnormal clinical laboratory tests, vitals signs, ECG parameters and injection site reactions) [ Time Frame: Admission up to 8 to 10 days post final dose ]
    Safety and Tolerability

  8. Part 3 Maximum observed plasma concentration (Cmax) of single subcutaneous doses of HTL0030310 [ Time Frame: Predose to 96 hours postdose ]
    Pharmacokinetics

  9. Part 3 Time to reach Maximum observed plasma concentration (Tmax) of single subcutaneous doses of HTL0030310 [ Time Frame: Predose to 96 hours postdose ]
    Pharmacokinetics

  10. Part 3 Area under the curve (AUC) of single subcutaneous doses of HTL0030310 [ Time Frame: Predose to 96 hours postdose ]
    Pharmacokinetics



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria

  1. Healthy males or healthy WONCBP; a woman is considered of childbearing potential unless she is permanently sterile (hysterectomy, bilateral salpingectomy and bilateral oophorectomy) or is postmenopausal (had no menses for 12 months without an alternative medical cause and a serum follicle-stimulating hormone [FSH] concentration ≥40 IU/L).
  2. Age 18 to 50 years of age
  3. A BMI of 20.0 to 30.0 kg/m2, with a minimum weight of 45 kg
  4. Must be willing and able to communicate and participate in the whole study
  5. Must provide written informed consent
  6. Must agree to adhere to the contraception requirements defined in the protocol (Section 9.4) Inclusion criteria 4 and 6 from the list above will be re-assessed at admission/pre-dose.

Exclusion Criteria

  1. Subjects who have received any IMP in a clinical research study within the previous 3 months of screening
  2. Subjects who are study site employees, or immediate family members of a study site or sponsor employee
  3. Subjects who have previously been enrolled in this study. Subjects who have taken part in Part 1/Part 2 are not permitted to take part in Part 2/Part 3
  4. History of any drug or alcohol abuse in the past 2 years
  5. Regular alcohol consumption in males >21 units per week and females >14 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 Units = 125 mL glass of wine, depending on type)
  6. Current smokers and those who have smoked within the last 12 months. A breath carbon monoxide reading of greater than 10 ppm at screening and admission
  7. Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months
  8. Females of childbearing potential. A woman is considered of childbearing potential unless she is permanently sterile (hysterectomy, bilateral salpingectomy and bilateral oophorectomy) or is postmenopausal (had no menses for 12 months without an alternative medical cause and a serum FSH concentration ≥40 IU/L). All female subjects must have a negative urine pregnancy test
  9. Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator at screening
  10. Subjects with vital signs outside the normal range for healthy volunteers (HR < 50 or >90 bpm; Systolic BP > 140 mmHg; Diastolic BP > 90 mmHg)
  11. Clinically significant abnormal biochemistry, haematology, coagulation or urinalysis as judged by the investigator (laboratory parameters are listed in Appendix 1 of the protocol)
  12. Fasting blood glucose at screening above the upper limit of normal (3.9 to 5.8 mM)
  13. HbA1c at screening above the upper limit of normal (>6%)
  14. Abnormal renal function - defined as creatinine clearance < 70mL/min using the Cockcroft-Gault equation at screening
  15. Abnormal hepatic function - defined as ALT, AST and total bilirubin > 1.5 x upper limit of normal at screening
  16. Positive drugs of abuse test result (drugs of abuse tests are listed in Appendix 1 of the protocol)
  17. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results
  18. History of clinically significant cardiovascular, renal, hepatic, chronic respiratory or GI disease, neurological or psychiatric disorder, as judged by the investigator
  19. Family history of long QT syndrome or sudden cardiac death in a young adult where a cause of arrhythmia cannot be excluded
  20. QTcF at screening >450 msec in males or >470 msec in females
  21. Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients, including glucose/fructose intolerance for the standard OGTT
  22. Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hayfever is allowed unless it is active
  23. Donation or loss of greater than 400 mL of blood within the previous 3 months
  24. Subjects who are taking, or have taken, any prescribed or over-the-counter drug (other than up to 4 g per day paracetamol) or herbal remedies (including St. John's Wort) in the 21 days before IMP administration (See Section 11.4 of protocol). Exceptions may apply on a case by case basis, if considered not to interfere with the objectives of the study, as agreed by the PI and sponsor's medical monitor
  25. Subjects with tattoos or scars on the abdomen which may interfere with injection site assessments or pharmacodynamic measurements, as determined by the PI or delegate at screening
  26. Failure to satisfy the investigator of fitness to participate for any other reason Exclusion criteria 11, 16, 22, 24 and 26 from the list above will be re-assessed at admission/pre-dose.

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): NCT03847207


Locations
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United Kingdom
Quotient Sciences
Nottingham, United Kingdom, NG11 6JS
Sponsors and Collaborators
Heptares Therapeutics Limited
Investigators
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Principal Investigator: Philip Evans, MBChB Quotient Sciences

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Responsible Party: Heptares Therapeutics Limited
ClinicalTrials.gov Identifier: NCT03847207     History of Changes
Other Study ID Numbers: HTL0030310-101
2018-003169-33 ( EudraCT Number )
QSC200729 ( Other Identifier: Quotient Sciences )
First Posted: February 20, 2019    Key Record Dates
Last Update Posted: August 8, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Heptares Therapeutics Limited:
First in Human
Single Ascending Dose
Additional relevant MeSH terms:
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Pasireotide
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs