Clinical trial NCT03302845: A Phase 1 Study to Evaluate the Effects of Omeprazole and Famotidine on the Absorption of Telotristat Ethyl in Healthy Subjects
Official title: A Phase 1, Open-label, Parallel Group, Drug-drug Pharmacokinetic Interaction Study to Evaluate the Effects of Multiple-dose Omeprazole and Famotidine on the Absorption of Single-dose Telotristat Ethyl in Healthy Male and Female Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Drug-drug Interaction
Lead sponsor: Lexicon Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2017-10-05
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: This drug-drug interaction study will evaluate the impact of two different acid reducing agents (from two different drug classes) co-administered with a single dose of telotristat ethyl.


Eligibility criteria: Inclusion Criteria:

* Healthy adult males or females ≥18 to ≤ 65 years of age at the time of Screening:

  1. Females of non-childbearing potential are to be surgically sterile (documented hysterectomy, tubal ligation, or bilateral salpingo-oophorectomy) or postmenopausal (defined as at least 12 months of spontaneous amenorrhea). Females of childbearing potential must agree to use an adequate method of contraception during the study from CRU admission through Safety Follow-up. Adequate methods of contraception for subjects or partner include condom, diaphragm, or cervical cap used in conjunction with spermicidal gel, foam, cream, film, or suppository. Hormonal contraception is NOT acceptable in this study. If necessary, follicle-stimulating hormone (FSH) results \>40 IU/L at Screening are confirmatory in the absence of a clear postmenopausal history.
  2. Nonsterile male subjects with sexual partners of childbearing potential must agree to use adequate methods of contraception from CRU admission through Safety Follow-up. Adequate methods of contraception for subjects or partner include the following: condom with spermicidal gel, diaphragm with spermicidal gel, coil (intrauterine device), surgical sterilization, vasectomy, oral contraceptive pill, depo-progesterone injections, progesterone implant (ie, Implanon®), NuvaRing®, Ortho Evra®; if a subject is not sexually active, but becomes active, he or his partner should use medically accepted forms of contraception.
* Body mass index ≥18.0 to ≤32.0 kg/m2 at Screening and Baseline/predose Day 1
* Willing to adhere to the prohibitions and restrictions specified in this protocol
* Able to comprehend and willing to sign an informed consent form (ICF)
* All laboratory values at Screening and CRU admission fall within normal range or are evaluated as not clinically significant (NCS) by the Investigator if outside normal range.
* Has no clinically meaningful abnormal findings during Screening and CRU admission physical examination, Screening and Baseline ECG, or Screening and Baseline vital signs
* Has the ability to understand and communicate the requirements of the study and is willing to comply with all study procedures
* Has not consumed and agrees to abstain from taking any dietary supplements, herbal products (eg, St. John's wort, garlic, or milk thistle), over-the-counter medications (OTC), supratherapeutic doses of vitamins, or prescription drugs (except as authorized by the Investigator AND Medical Monitor) from 14 days prior to CRU admission through the Safety Follow-up Visit
* Has not consumed alcohol-containing beverages for 3 days prior to CRU admission (as confirmed by alcohol breath analyzer) and agrees not to consume alcohol through the Safety Follow-up Visit
* Has not used tobacco- and/or nicotine-containing products within 60 days prior to the CRU admission and agrees to abstain from using tobacco- and/or nicotine-containing products, including e-cigarettes, through the Safety Follow-up Visit

Exclusion Criteria:

* History of any clinically significant psychiatric, renal, hepatic, pancreatic, cardiovascular, neurological, endocrinologic, hematological, or gastrointestinal (GI) abnormality
* Participation in another investigational study within 30 days of CRU admission
* Receipt of any protein- or antibody-based therapeutic agents (eg, growth hormones or monoclonal antibodies) within 3 months prior to Screening. Note: Influenza vaccine will be allowed if administered \>21 days prior to CRU admission.
* Prior exposure to TE
* History of any serious adverse reaction or hypersensitivity to any inactive component of TE (ie, microcrystalline cellulose, croscarmellose sodium \[disintegrant\], talc, silicone dioxide, and magnesium stearate \[non-bovine\]), unless reaction is deemed irrelevant to the study by the Investigator and Sponsor
* History of malabsorption, bariatric surgery, gastric surgery, cholecystectomy, short-bowel syndrome, or GI surgery that may induce malabsorption
* History of any serious adverse reaction or hypersensitivity to any component of OMP or FTE
* History of any active infection within 14 days prior to first drug administration, if deemed clinically significant by the Investigator and/or Sponsor
* Positive hepatitis panel (including hepatitis B surface antigen and hepatitis C virus antibody) or positive human immunodeficiency virus antibody screens
* Existence of any surgical or medical condition that, in the judgment of the Investigator, might interfere with the absorption, distribution, metabolism, or excretion of TE (appendectomy and hernia repair are acceptable)
* Concurrent conditions that could interfere with safety and/or tolerability measurements
* Subject has donated plasma within 7 days of first drug administration.
* Subject has donated 1 or more pints of blood (or equivalent blood loss) within 30 days prior to first drug administration.
* Women who are breastfeeding or are planning to become pregnant during the study
* eGFR ≤ 89 ml/min/1.73 m2
* Positive pregnancy test (females only)
* Positive urine screen for selected drugs of abuse and cotinine at Screening or CRU admission
* Consumption of caffeine- and/or xanthine-containing products (cola, coffee, tea, chocolate, etc.) within 72 hours prior to CRU admission (Day 0) and throughout the study
* Consumption of grapefruit, Seville oranges, and grapefruit- or Seville orange-containing products within 72 hours prior to CRU admission (Day 0) and throughout the study
* Need for dietary restrictions, unless the restrictions are approved by the Investigator and Sponsor
* Inability or difficulty swallowing whole tablets
* Poor venous access as defined by the Investigator or a designee
* Any other condition that compromises the ability of the subject to provide informed consent or to comply with the objectives and procedures of this protocol, as judged by the Investigator or medical monitor
* Unable or unwilling to communicate or cooperate with the Investigator for any reason
* Employee of the Investigator or study center, with direct involvement in the proposed study or other studies under the direction of that Investigator or study center, as well as family members of the employees or the Investigator

Primary outcomes:
measure: Maximum observed concentration of telotristat ethyl
timeFrame: 7 days
measure: Time of maximum observed concentration of telotristat ethyl
timeFrame: 7 days
measure: Area under the plasma concentration-time curve beginning from the first dose until the last quantifiable concentration of telotristat ethyl
timeFrame: 7 days
Secondary outcomes:
measure: Number of adverse events
timeFrame: Up to 13 days
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Covance Clinical Research Unit
state: Texas
Study officials:
affiliation: Lexicon Pharmaceuticals, Inc.
name: Suman Wason, MD
role: STUDY_DIRECTOR
References: